The long non-coding RNA CASC15 (CASC15) is considered as a tumor-related lncRNA involved in regulating biological processes such as proliferation, invasion and migration of a variety of tumor cells. However, the role of CASC15 in intracellular lipid metabolism remains unclear. The sterol-regulatory element binding proteins 1 (SREBP1) is a key transcription factor that regulates lipid metabolism in cells, and its member SREBP1a mainly regulates the expression of key enzyme genes in lipid synthesis. In this paper, we investigated the effects of CASC15 on the expression and localization of lipid regulator SREBP1a in human liver cells through molecular biology and cell function experiments. The results showed that in liver cells, the mRNA and total protein levels of intracellular SREBP1a remained unchanged after overexpression of CASC15 (P<0.001), while the precursor protein levels increased (P<0.05) with enhanced translocation into the nucleus; However, the levels of fatty acid synthesis-related products free fatty acids (P<0.001) and triglycerides (P<0.001) regulated by SREBP1a showed a down-regulation trend. This paper reveals a possible mechanism by which CASC15 regulates lipid metabolism in liver cells, hoping to provide new ideas for the treatment and research of diseases related to lipid metabolism disorders.

MicroRNAs (miRNA) are non-coding RNAs with short sequences that play important regulatory roles in biological process such as cell proliferation, differentiation and apoptosis. The occurrence and development of many diseases are related to abnormal expression of miRNA. Therefore, accurate detection of relevant miRNA at the early stage of disease occurrence will contribute to early diagnosis and timely treatment of diseases. Nucleic acid biosensors have been widely applied in detection due to stable chemical properties, simple design, easy modification and programmability. The G-quadruplex functional nucleic acids are special spatial structure formed by guanine-rich DNA through Hoogsteen hydrogen bonds. The G-quadruplex has been widely used in miRNA detection because it can interact with some small molecules such as porphyrin, fluorescein and hemin to enhance their physicochemical properties through Van der Waals forces andhydrophobic interaction and other interactions. At present, the G-quadruplex has been combined with nucleic acid amplification or nano-signal amplification technology to improve sensitivity, which can be used for target recognition and auxiliary signal output. Firstly, this paper introduced the structure of G-quadruplex and the mechanism to enhance fluorescence and increase enzyme-like activity. Secondly, according to the above characteristics, the research progress of G-quadruplex combined with fluorescent ligands to construct miRNA fluorescent biosensors, and the miRNA biosensing platform based on G-quadruplex/hemin in colorimetric, electrochemistry and chemiluminescence detection were discussed. Finally, the challenges faced by G-quadruplexes in miRNA detection were discussed, and the future development trend was prospected. This review may help to promote the construction of nucleic acid biosensors with high sensitivity and specificity.

MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in regulating target genes in stress response and biotic stress in plants. It is unclear whether endogenous miR167 of Pinellia ternate is involved in virus stress. In this study, the endogenous miR167 of Pinellia ternate was firstly amplified and named pt-miR167. The conservative analysis, phylogenetic analysis and target gene prediction were carried out using bioinformatics software. On this basis, qRT-PCR was used to detect the accumulation of soybean mosaic virus(SMV), the expression level of miR167 and its potential target genes, analysis of miR167 and target gene expression patterns in response to viral infection. The results showed that the virus accumulation increased rapidly at 5~15 d, with the fastest increase at 10 d, and then showed a slow upward trend. After virus infection, compared with the control group, the expression of pt-miR167 was down-regulated, and the expression was the lowest at 10 d. Evolutionary tree analysis shows that, pt-miR167 is highly homologous to sly-miR167a in tomato (Solanum lycopersicum). The predicted expression of ARF6 target genes is in the opposite trend to that of pt-miR167, and its expression reached the highest level at 10 d. This study shows that miRNA participates in the interaction between the host and the virus. The results are helpful to reveal the interaction mechanism between SMV and the host Pinellia ternate. It will provide a reference for further studies of viruses and plants in the future, and a research basis for the production of Pinellia ternate.

Circular RNA (circRNA) are a class of single-stranded covalently closed RNA molecules formed by back-splicing. It can regulate various life activities through sponge microRNA(miRNA), bind to RNA-binding protein (RBP), and regulate gene expression. In addition, circRNA can also perform translation activities and is considered to be a promising biomarker. N⁶-methyladenosine(m⁶A) is the most widespread and most common way of RNA modification in eukaryotes. It functions through three types of regulators: m⁶A methyltransferases (writers), m⁶A demethylases (erasers) and m⁶A recognition proteins (readers). In addition to its role in mRNA, m⁶A also has a regulatory role in circRNA. m⁶A modification can regulate the expression, stability, cytoplasmic transfer, translation, and evasion of innate immunity of circRNA, and it has been found to be involved in colorectal cancer, liver cancer, non-small cell lung cancer, cervical cancer, breast cancer, osteosarcoma, hypopharyngeal squamous cell carcinoma, pancreatic ductal adenocarcinoma, gastric cancer and other tumors. In addition, m⁶A modifications have been found to regulate immune responses. In this paper, the regulatory mechanism of m⁶A modification based on circRNA was reviewed, the regulatory role of m⁶A modified circRNA in various tumors and immune responses was expounded, and the effect of m⁶A modified circRNA on immune response was discussed. m⁶A modification may enhance circRNAs as biomarkers in multiple ways, and put forward a new perspective for the diagnosis, treatment and prognosis of diseases based on m⁶A modification of circRNA in the future.

Recent studies have shown that long-term heavy smoking can cause irreversible damage to the testis and then block spermatogenesis, in which the apoptotic signaling pathway plays a key role. However, its molecular regulation mechanism remains to be further studied. The purpose of this study is to explore the targeting regulation mechanism of miRNA-138-5p in the injury of testicular Sertoli cells (TM4) induced by cigarette smoking. The MTT assay, lactate dehydrogenase (LDH) assay and TUNEL assay showed that after cigarette smoke exposure (CSE) intervention, the survival rate of TM4 cells was significantly decreased (P<0.05), LDH activity was significantly increased (P<0.05), and apoptosis rate was significantly increased (P<0.05). RT-PCR and Western blotting results showed that the mRNA and protein expression levels of p53, Bak and caspase-3 were significantly up-regulated after 10% CSE intervention (P<0.05). CSE intervention was also performed after transfection of miRNA-138-5p overexpression plasmids. The results showed that the survival rate of Sertoli cells was significantly increased (P<0.05), the number of apoptotic positive cells was significantly decreased (P<0.05), and the mRNA and protein expressions of p53, Bak and caspase-3 were significantly down-regulated compared with those before transfection (P<0.05). After silencing miRNA-138-5p, the mRNA and protein expression levels of Bak and Caspase-3 were significantly increased (P < 0.05). Online database analysis showed that miRNA-138-5p and caspase-3 had high matching prediction values. The double luciferase reporter gene results showed that Bak did not bind to miRNA-138-5p, while caspase-3 could bind to miRNA-138-5p. These results suggest that miRNA-138-5p can target the regulation of Caspase-3 and slow down the apoptosis of Sertoli cells induced by cigarette smoking, which has a protective effect on Sertoli cells.

In recent years, it has been found that microRNA (miRNA) carried by exosomes play an important role in the development of tissue and organ fibrosis. However, studies on the relationship between radiation-induced cardiac fibrosis (RICF) and exosomes and their miRNA are very limited. The purpose of this study is to analyze the possible role of radiation-induced exosome miRNA in the development of RICF by bioinformatics. Myocardial fibroblasts (CFs) are the main effector cells of RICF. The CFs were irradiated with 2 Gy X-rays, and radiation-induced exosomes (X-exo) and unirradiated exosomes of CFs (Exo) were extracted by overspeed centrifugation. Then, exosomes were observed and identified with its morphology, NTA concentration, and exosome surface marker proteins such as CD9, CD63, and CD81. Subsequently, RNA-seq technology was used to detect the miRNA expression profiles of Exo and X-exo, then the differentially expressed miRNAs were screened and their potential target genes and enrichment analysis were analyzed. The results showed that, compared with the control group (Exo), 9 miRNAs were up-regulated in the X-exo (|log₂ Fold Change|>1, P<0.05), of these, 8 are the ones with |log₂ Fold Change|>2; 19 miRNAs were down-regulated in the X-exo (|log₂ Fold Change|>1, P<0.05), of these, 12 are the ones with |log₂ Fold Change|>2. TargetScan, miRWalk and miRNADB were used to predict the target genes of differentially expressed miRNAs, and GO and KEGG enrichment analysis were performed. GO enrichment results showed that target genes regulated by differentially expressed miRNAs were mainly involved in biological processes such as protein phosphorylation and cell signal transduction. Those differentially expressed miRNAs were enriched in cytoplasm, cell membrane and other cellular components, playing molecular functions such as protein kinase binding and protein binding. KEGG enrichment results showed that target genes with differentially expressed miRNAs were mainly enriched in PI3K-Akt, MAPK, mTOR, ECM-receptor interaction, cAMP, Wnt, TGF-β and Notch related signaling pathways. Combing with literatures, it is suggested that differentially expressed exosomal miRNA may promote the development of RICF by regulating the target genes and related signaling pathways. Because the activation regulation of signaling pathways such as MAPK, PI3K/AKT, and mTOR are mainly dependent on the phosphorylation of key molecules, but not on the regulation of the transcriptional level. The detailed mechanism of "Exosomes miRNA mediate radiation bystander effects to promote RICF" will be investigated in future studies, and the signaling pathways such as ECM, cAMP, TGF-β, Wnt, Notch, Ras, and Rap1 should be the focus.

Hypertrophic cardiomyopathy (HCM) is a kind of primary cardiomyopathy characterized by hypertrophic cardiomyocytes. The molecular mechanism of its pathogenesis has not been clearly defined. This study integrates the data sets numbered GSE130036 and GSE36946 in the Gene Expression Omnibus (GEO) database. The expression difference analysis of RNA expression matrix in the data set are performed by R language. The biological function enrichment analysis of differentially expressed mRNAs was carried out, and the chromatin remodeling factor BPTF (bromodomain PHD finger transcription factor) was identified. The binding sites of miRNA targeting mRNA and lncRNA were predicted with BPTF as the core, and the endogenous competitive RNA (ceRNA) network of lncRNA TNRC6CAS1-miR-30c-1-3p-BPTF was constructed. The expression of BPTF and lncRNA TNRC6CAS1 was significantly up-regulated (P<0.001), while the expression of miR-30c-1-3p was significantly down-regulated (P<0.001) in HCM clinical samples (peripheral blood of 20 healthy people and 20 hypertrophic cardiomyopathy patients) and myocardial hypertrophy cell models using real-time quantitative PCR, enzyme-linked immunosorbent assay or immunoblotting experiments. The correlation of the three molecular expressions was preliminarily verified in AC16 cells. Finally, silencing BPTF, lncRNA TNRC6CAS1 or overexpressing miR-30c-1-3p could inhibit the expression of cardiac hypertrophy marker proteins. The above results indicated that the ceRNA network composed of lncRNA TNRC6CAS1, miR-30c-1-3p, and BPTF may participate in regulating the generation of cardiac hypertrophy in HCM. As potential pathogenic molecules of HCM, the three molecules are expected to become new diagnostic and treatment targets.

Melanoma is a malignant tumor that occurs frequently in the skin. Due to its strong invasiveness and poor prognosis, it has always been the researchers' focus. Circular RNAs (circRNAs) are novel endogenous non-coding RNAs, which are widely involved in animal growth and development, cell differentiation, signal transduction and other physiological processes. However, the molecular mechanism of circRNAs in melanoma cells has not been fully analyzed. In this study, mice (C57BL/6J) normal melanocytes and B16 melanoma cells were used as research objects, and the expression characteristics of circRNAs between the two kinds of cells were analyzed by second-generation sequencing technology. Sequencing results showed that there were 851 circRNAs and 195 differentially expressed circRNAs (DECs) in mouse normal and melanoma cells. GO and KEGG database annotation found that the source genes of DECs were mainly involved in the cell cycle, the tight junction, the Rap1 signaling pathway, the TGF-beta signaling pathway and other signaling pathways related to cell proliferation and migration. CircE2F5 (circ-3:14578602|14606309) was significantly overexpressed in melanoma cells compared with normal melanocyte, which could increase E2F5 expression, promote the melanoma cell proliferation. TargetScan 7.0 and RegRNA 2.0 predicted that there were 73 DECs in mouse normal melanocytes and melanoma cells that had miRNA binding sites, and multiple potentially targeted miRNAs were involved in the proliferation and migration of melanocytes. In sum, multiple DECs related to melanoma cell proliferation and migration were obtained by functional annotation of DEC source genes and potential targeted miRNAs of DECs, and we expected it to provide new insights for melanoma research.

Statins can bring some benefits to the treatment of diabetic cardiomyopathy (DCM), but the specific molecular pathway of their action is still unclear. Recent studies have shown that abnormal expression of long noncoding RNA (lncRNA) is closely related to the pathological development of DCM. To compare the degree of myocardial injury between diabetic rats treated with rosuvastatin and rats treated with conventional therapy, the therapeutic pathway and potential target of rosuvastatin on DCM was investigated. Total RNA of DCM rats was extracted and 1ncRNA microarray was prepared to screen out differentially expressed 1ncRNA and bioinformatics analysis was carried out. The results showed that 770 target genes were up-regulated and 884 were down-regulated in the treatment group compared with the model group, which were mainly related to improvement of metabolic disorder, regulation of the ratio of myocardial cells to collagen fibers, reduction of myocardial injury and exercise burden, prevention of autonomic nervous system and microcirculation diseases and change of eating habits. The signaling pathways involved are mainly concentrated in sensory pathways, signal transduction, lipid metabolism and so on. It is suggested that rosuvastatin may play a role in the treatment of DCM by regulating the participation of 1ncRNA in glucose and lipid energy metabolism and ion balance, inhibiting the process of myocardial fibrosis and improving the effect of high glucose toxicity on autonomic nervous function.

In this study, we performed high-throughput sequencing technology methylated RNA immunoprecipitation sequencing (MeRIP-seq), transcriptome sequencing (RNA-seq) and bioinformatics to analyze the differentially m6A-methylated and differentially expressed profile of circular RNA (circRNA) in middle cerebral artery occlusion / reperfusion (MCAO/R) model, which provided some scientific evidences for revealing the relationship between RNA epigenetic modification and cerebral ischemia reperfusion injury. The neurological deficit scores of mice were evaluated by the Longa score standard. TTC staining was used to detect cerebral infarction volumes, and dot blot was used for the quantification of m⁶A abundance. The results showed that the MCAO/R group showed severe neurological loss, and their Longa scores (2.75 ± 0.25) were significantly increased compared with that in the sham group. The percentage of cerebral infarct volumes in the MCAO/R group (27.63％ ± 4.24%) was higher than that in the sham group and cerebral ischemia-reperfusion elevated global m⁶A levels. Compared with the sham group, 1787 circRNAs in the MCAO/R group were significantly changed, of which 852 circRNAs were increased and 935 circRNAs were decreased significantly (P<0.05). Gene ontology (GO) function analysis showed that differentially target genes were mainly involved in translation, protein N-linked glycosylation, response to hormone, interleukin-6-mediated signaling pathway, Golgi cisterna membrane, and integral component of endoplasmic reticulum membrane, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that differential circRNAs were mainly related to N-Glycan biosynthesis, Wnt signaling pathway, gastric acid secretion, glutamatergic synapse, phospholipase D signaling pathway, taste transduction, african trypanosomiasis, thyroid hormone synthesis, insulin secretion and so on. Compared with the sham group, 22 m6A peaks in the MCAO/R group were significantly changed, of which 14 m6A peaks were significantly upregulated and 8 m6A peaks were decreased significantly(P<0.05). GO and KEGG pathway analyses of the predicted target genes of the differentially m6A-methylated circRNAs were performed. GO analysis showed that differentially m6A-methylated target genes were mainly related to 5-methylcytosine catabolic process, chemical homeostasis within a tissue, G-protein coupled glutamate receptor binding and so on. KEGG pathway enrichment analysis indicated that the differentially m⁶A-methylated circRNAs target genes were mainly related to Fanconi anemia pathway. By comprehensively analyzing MeRIP-seq and RNA-seq data, there were seven differentially m⁶A-methylated and expressed circRNAs, and RT-qPCR was used to detect their expression. The target genes of the differentially m6A-methylated and differentially expressed circRNAs were predicted. In this study, sequencing analysis of the differentially m⁶A-methylated and differentially expressed circRNAs from sham and MCAO/R groups, and the results suggest that cerebral ischemia-reperfusion can cause changes of the circRNA expression profile and m⁶A modification profile in mice, and target genes of differentially expressed circRNA and differentially methylated circRNA are involved in multiple functions and pathways. This study lays the foundation for revealing the molecular mechanism of cerebral ischemia-reperfusion injury from epigenetic level and provides potential target sites for subsequent research on cerebral ischemia-reperfusion injury.

Long non-coding RNA (lncRNA) is a type of non-coding RNA with the more than 200 nucleotides. Several lncRNAs have been identified as the potential targets for cancer therapy. LncRNA00067110 is one of the differentially expressed genes in the transcriptome profiles of melanoma B16-F10 cells compared to normal mice melanocytes. To investigate whether lncRNA00067110 regulates the proliferation, apoptosis and melanogenesis of B16-F10 cells, the calcium-binding tyrosine phosphorylation regulated protein (Cabyr) target gene was predicted by LncTar and verified by dual luciferase activities. The regulating function of lncRNA00067110 was investigated by the analysis of transcriptome profiles and to detect the proliferation, apoptosis and melanin production of B16-F10 cells transfected by the overexpression plasmids of lncRNA00067110. The results showed that the relationship of lncRNA00067110 targeting Cabyr, the mRNA and protein levels of proliferation (MEK/ERK/ MNK/ CREB) and melanogenesis-related genes (TYR family and CREB) were significantly down-regulated, while the mRNA and protein levels of apoptosis-related genes (AKT and Bcl-2) were up-regulated in B16-F10 cells with lncRNA00067110 overexpression. The transcriptome profile of B16-F10 cells with lncRNA00067110 overexpression showed that 17 genes were differentially expressed, among which Cabyr was up-regulated. Furthermore, the effect of lncRNA00067110 on the phenotypes of cell proliferation and apoptosis were verified. The results suggested that lncRNA00067110 might be a novel target for the treatment of melanoma by targeting Cabyr, which regulate the expression of related genes to inhibit the proliferation and melanogenesis, as well as to induce the apoptosis of B16-F10 cells.

With the development of sequencing technology and in-depth research on tRNA-derived small molecules (tsRNAs), more and more tRNAs and their functions have been identified in various species. tsRNAs can be divided into tRNA-derived fragment (tRF) and tRNA-derived stress-induced RNA (tiRNA) according to different cleavage sites. And we will focus on tRF, which is a kind of non-coding RNA with regulatory function. To deepen the research of tRF, a large number of tRF identification methods based on sequencing data and corresponding databases are being constructed in recent years. The former mainly includes the method of Telonis et al. and tDRmapper, while the latter mainly includes tRFdb, tRF2Cancer and MINTbase. At the same time, both provide a more effective tool for the in-depth research of tRF. The regulation mechanisms of tRF are also being illustrated in many studies. tRF mainly regulates the expression of RNA, DNA and proteins in a miRNA-like manner. With further investigations, researchers have found that tRF also plays a specific regulatory role in various biological processes of human diseases, suggesting its role as a potential biomarker. Herein we mainly summarize the identification methods, databases, regulation mechanisms of tRF and its role in human diseases.

Circular RNA (circRNA), as a competitive endogenous RNA (ceRNA), plays an important role in the regulation of cell differentiation. The purpose of this study was to identify and analyze porcine circular RNA insulin-like growth factor 1 receptor (circIGF1R), explore its expression patterns, construct a ceRNA regulatory network related to circIGF1R, and explore the regulation of its ectopic expression on adipogenic differentiation of mouse mesenchymal stem cells (C3H10T1/2) effect. Forward and reverse PCR, Sanger sequencing, RNase R enzyme digestion tests, and qRT-PCR were used to verify that circIGF1R is a circRNA formed by the second exon of insulin-like growth factor 1 receptor (IGF1R). It was expressed in all tissues of pigs, and its expression level increased with age in adipose tissues. miRDB, TargetScan and miRWalk online software were used to predict circIGF1R target genes. RNAhybrid software was used for binding site prediction. DAVID bioinformatics functional analysis software was used to perform GO and KEGG enrichment analysis on candidate target genes. Cytoscape software was used to construct the ceRNA network diagram. Based on the gene expression correlation and predicted target relationship, the GO and KEGG enrichment analysis was drawn and the ceRNA network was constructed; the dual luciferase reporter gene test was used, and we found that circIGF1R and FABP4 can bind to ssc (Sus scrofa chromosome) -miR-133a-5p. The circIGF1R overexpression vector was successfully constructed and expressed in C3H10T1/2 cells. It was found that after overexpression of circIGF1R, the expression of key adipogenic regulatory factors CEBPα, CEBPβ, FABP4 and PPARγ increased significantly(P＜0.01), and the number of lipid droplets increased significantly. The results of this study show that circIGF1R exists in pig adipose tissues, and may positively regulate the adipogenic differentiation of C3H10T1/2 cells through the ceRNA mechanism, which lays a theoretical foundation for further research on circIGF1R regulating the adipogenic differentiation of pig precursor intramuscular adipocytes.

In this study, high-throughput sequencing technology was used to analyze the differentially expressed microRNA (miRNA) of astrocyte-derived exosomes in control group and oxygen and glucose deprivation/reoxygenation (OGD/R) group. Ultracentrifugation was used to extract exosomes from the supernatant of astrocyte medium in the control group and OGD/R group. Transmission electron microscopy showed that exosomes had a typicalvesicle shape with intact membrane and low electron content density. Nanoparticle tracking technology (NTA) detected astrocyte exosomes with a size of 100.5±31.1 nm, accounting for 96.8%. Western blot detection showed that the exosome contained exosome-specific proteins tumor-susceptibility protein (TSG101), heat shock protein 60 (Hsp60), ALG-2-interacting protein X (ALIX). Compared with the control group, 41 miRNAs in the exosomes of the OGD/R group were significantly changed, of which 20 miRNAs were increased and 21 miRNAs were decreased significantly (P<0.05). Gene ontology function (GO) analysis showed that significantly differentially target genes were mainly involved in protein glycosylation, lipid metabolism, phosphorylation, Golgi apparatus, endoplasmic reticulum, endosome, cytoplasmic vesicles and cell protrusions , etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that differential miRNAs were mainly related to metabolic pathways and signaling pathways such as butyrate metabolism, β-alanine metabolism, fatty acid degradation, mitophagy and P53 signaling pathway. Sequencing analysis of the exosomal miRNAs derived from control and OGD/R astrocytes and target gene function enrichment analysis can be useful for the mechanism study of astrocyte exosomes in response to oxygen and glucose deprivation reperfusion.

Developmental programming of the embryo is controlled by both genetic information and epigenetic information. During fertilization, this information carried by sperms can be delivered to the zygote, where they can regulate early embryonic development. Mature sperms are highly abundant in epigenetic information, and including small non-coding RNAs (sncRNAs), which play important roles during spermatogenesis, fertilization, and early embryo development. Recent studies revealed that sncRNAs can regulate gene expression, mediate protein translation, transmit the epigenetic information, and so on. Recently, increasing evidences showed that parental environment exposure, such as diet, toxicant, pressure, may cause the inheritance of acquired characteristics, and they can be stored and transmitted to the next generation by epigenetic information in germ cells. Recent advances of transgenerational inheritance revealed that sncRNAs are environmentally responsive epigenetic molecules in sperms. This review summarized current knowledge about the sncRNAs information in sperms, including transfer RNA-derived small RNAs (tsRNAs), rsRNAs (risbosome-RNA derived small RNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), that are responsive to environmental factors and are capable of affecting embryonic development and the phenotype of the offspring later in life. Furthermore, this review also delineated potential molecular mechanisms that might regulate sperm sncRNAs.

As an important member of the non-coding RNA family, circRNA is a kind of single-stranded RNA with a covalently closed loop structure without a polyadenylated acid tail and 5′-3′ end, showing high stability, abundance and conservation across species characteristics. Recent studies have shown that circRNA plays an important role in many biological processes, including chemotherapy resistance and malignant progression. Exosomes are small extracellular phospholipid bilayer vesicles with a diameter of 30-150 nm that are secreted by living cells. They can be used as carriers to encapsulate and transfer functional molecules. Exosomes are important mediators of communication between tumor cells and stromal cells. They can play a role in the transmission of chemoresistance by transferring circRNA. As chemotherapy resistance is still a huge obstacle to the prognosis of cancer, the research of exosomal circRNA-mediated tumor chemotherapy resistance is at the forefront of academic research, which is a blue ocean with important significance. In this paper, we summarized the latest research progress in the aspects of exosome delivery of circRNA, the mechanism of exosome sorting non-coding RNA cargo, circRNA-mediated tumor chemotherapy resistance, exosome delivery of circRNA-mediated tumor chemotherapy resistance and its potential clinical application, which may provide a reference for the research of tumor chemotherapy resistance.

Circular RNA (circRNA) is a novel RNA with circular structures. It is conserved in various species, and characterized by high stability, high expression levels and tissue specificity. Meanwhile, it could serve as microRNA (miRNA) sponges, bind to RNA-binding proteins, or regulate transcription and protein translation. With the development of high-throughput sequencing and bioinformatics, circRNA was reported to participate in the pathogenesis of cancer. N6-methyladenosine (m6A) modification is the most common type of RNA modification in eukaryote RNA, which is a dynamic and reversible process regulated by m6A methyltransferase, m6A demethylase and m6A-binding proteins. M6A modification is involved in the regulation of RNA nuclear export, splicing, stability, translation and degradation, thus playing a key role in the occurrence and development of multiple human diseases, such as cancers, cardiovascular diseases. Recently, some researches demonstrated that m6A modification of circRNA was essential in the occurrence and development of malignant tumors, such as cervical cancer, colorectal carcinoma, hepatocellular carcinoma, non-small cell lung cancer, poorly differentiated adenocarcinoma of the stomach. In the current manuscript, we summarized the mechanism of m6A RNA modification, the roles of m6A modification in regulation of circRNA, and the effects of circRNA m6A modification on tumor. The potential clinical application value of m6A-modified circRNA was further discussed, as to provide some new ideas and ways for early diagnosis, clinical treatment and prognosis of tumors.

Diabetes is a clinical syndrome caused by a variety of factors. It often causes multiple system damage, leading to chronic progressive lesions of the eye, kidney, blood vessels, heart, nerves and other organs. At present, its etiology and pathogenesis are not fully clarified, and there is a lack of effective cure. Further exploration of the molecular regulatory mechanisms that drive diabetes and its complications, identifying specific biomarkers and molecular therapeutic targets, is undoubtedly an effective strategy to prevent the onset and development of diabetes and improve the quality of life of patients. Long non-coding RNA (lncRNA) is an important regulator of body normal activity and disease development. Abnormal expression and mutation are one of the main causes of diabetes and many other diseases. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a newly discovered lncRNA molecule in recent years. It has attracted much attention because of its important regulatory role and diverse biological effects in diabetes and its complications. This article summarizes the molecular regulation mechanism and related biological functions of lncRNA NEAT1 in diabetes and its complications in order to provide a new scientific reference for early prevention, diagnosis and molecular targeted therapy of diabetes.

Long non-coding RNA (lncRNA) are non-coding RNA (ncRNA) greater than 200nt in length, which were initially considered as transcriptional "junk" with no biological function. As research progressed, lncRNA were found to be involved in many biological regulatory processes, such as chromosome silencing, chromatin modification, transcriptional activation and interference. These biological regulatory processes are closely related to the structure and spatial and temporal specific expression of lncRNA. In addition, the corresponding regulatory mechanisms of lncRNA with different structures and locations are different. When lncRNA are located in the nucleus, they mostly regulate gene expression at the transcriptional level and epigenetically, including histone modifications, DNA methylation, chromosome remodeling and other modification processes. In contrast, lncRNA in the cytoplasm mostly play regulatory roles at the post-transcriptional and translational levels, and the mechanisms of action and functions of lncRNA vary among different organelles, all of which illustrate the importance of the location of lncRNA on their functional performance. In addition, exosomes are also rich in lncRNA, and these lncRNA can be delivered to the corresponding sensitive cells through intercellular communication to generate the corresponding regulatory mechanisms. In addition, aberrant expression of lncRNA in different structures is often a key factor in the development and progression of related diseases and cancers. Studying the enrichment of lncRNA in different subcellular structures can help understand the specific roles played by lncRNA in regulating body homeostasis, disease and cancer occurrence and development, as well as growth and development of plants and animals, as well as provide a new theoretical basis for subsequent studies on targeted therapies and improving animal production performance. This paper outlines the latest research progress on the different regulatory mechanisms of lncRNA in chromosomes, membraneless substructures, cytoplasm (endoplasmic reticulum, ribosomes, mitochondria, lysosomes), exosomes and other locations, as well as describes the processes of related diseases and cancers caused by lncRNA abnormalities within the corresponding structures. Finally, an outlook on lncRNA research is given with the aim of providing a corresponding theoretical basis for future studies.

MicroRNA (miRNA) is a class of endogenous non-coding single-stranded RNA molecules with a length of about 16~29 nucleotides. Widely found in eukaryotes, they play important regulatory roles in plant cell proliferation and differentiation, organ formation, metabolism, resistance to salt, temperature, drought, heavy metal stress, etc. Plant miRNA mainly affects plant growth and development by degrading target genes or inhibiting the expression of target genes at the translation level. At present, the research on the production and regulation of miRNA is relatively clear, and the specific roles and regulatory networks of miRNA in plant secondary metabolism and response to abiotic stress have also been identified, which lays the foundation for a full understanding of the molecular regulation of miRNA. In order to better understand the expression and regulation characteristics of miRNA and to interpret the regulatory network of miRNA in plant secondary metabolism and abiotic stress response, we review the molecular mechanisms of plant miRNAs in regulating the biosynthesis of various secondary metabolites (flavonoids, terpenoids, alkaloids) and responding to environmental stress (salt, high temperature, low temperature, drought, heavy metal stress),and summarize the regulatory roles of miRNA in secondary metabolism and abiotic stress, which will provide references for understanding the relationship between environmental stress and plant metabolism, for further studying the regulatory mechanism of miRNA in maintaining plant homeostasis, and for cultivating superior crop varieties.

Macrophage polarization is a process of phenotypic regulation based on the surrounding stimulus environment, which is generally polarized into two phenotypes, namely classical activated M1 macrophages and alternative activated M2 macrophages. In short, M1 macrophages are characterized as pro-inflammatory and anti-tumor; M2 macrophages are anti-inflammatory and pro-tumor. Macrophage polarization is considered to be a key regulator of human physiology and pathology processes, and its effectiveness depends on the coordinated expression of key factors, whose expression is finely regulated by microRNAs (miRNAs) at the post-transcriptional level. MicroRNAs are small non-coding RNAs that have the ability to regulate gene expression and cellular network processes. More and more evidence shows that miRNAs play an important role in regulating macrophage polarization. Therefore, in this review, miRNAs regulating macrophage polarization to M1/M2 type and have bidirectional regulation function are listed, and how they regulate macrophage polarization through transcription factors and their potential in the treatment of inflammation and tumor.

Endoplasmic reticulum stress (ERS) is a cellular defensive response to restore homeostasis and reduce the protein load. Over-activation of ERS can induce cell differentiation, proliferation, apoptosis, and autophagy. MicroRNAs (miRNAs) are endogenous non-coding RNAs (ncRNAs) that regulate the expression of key proteins and genes in the ERS signaling pathway through post-transcriptional action. Meanwhile, activated ERS signaling pathway can indirectly regulate the expression and function of target genes by decreasing miRNA stability. Based on a brief introduction of ERS classical signaling pathways, this paper further elaborated how microRNAs regulate ERS signaling pathways to promote apoptosis and proliferation, and what effect they would have on the expression profile of diseases based on this association. We also summarize the regulation of ERS on miRNAs expression and the current research status. The mutual regulation between the two could provide a new idea for the follow-up research on the therapeutic targets of diseases.

Long non-coding RNAs (LncRNAs) are abnormally expressed in a variety of tumors and participate in the occurrence and development of tumors. However, the expression and function of many LncRNAs in tumors have not been fully clarified. In this paper, 113 normal breast tissues and 1 109 breast cancer tissues were analyzed in TCGT database. LncRNA AL133467.1 was found to be lowly expressed in breast cancer tissues and negatively correlated with poor prognosis of breast cancer patients. The expression of AL133467.1 in breast cancer cells was significantly lower than that in normal breast epithelial cells. We overexpressed AL133467.1 in relatively low-expression breast cancer cells SKBR3 and BT474, and cell count and plate colony-formation experiments showed that overexpression of AL133467.1 could significantly inhibit the proliferation and colony formation of breast cancer cells (P<0.01). Cell scratch and Transwell assays showed that the migration and invasion ability of breast cancer cells overexpressing AL133467.1 was significantly reduced compared with the control group (P<0.01). MiRDB database showed that AL133467.1 had binding sites with miR-661. miR-661 could bind the transducer of ErbB2, 2 (ErbB2, 2, TOB2). qRT-PCR showed that miR-661 was highly expressed in breast cancer cells and positively correlated with poor prognosis of breast cancer patients (P<0.001). Luciferase reporter assays showed that AL133467.1 had specific binding to miR-661 (P<0.01). AL133467.1 overexpression could inhibit the expression of miR-661 in breast cancer cells (P<0.0001). Transfection of miR-661 mimics eliminated the inhibitory effect of overexpression of AL133467.1 on breast cancer cells (P<0.001). In addition, qRT-PCR and Western blotting results showed that overexpression of AL133467.1 up-regulated TOB2 mRNA (P<0.0001) and protein levels. But when miR-661 mimics were transfected, TOB2 mRNA (P<0.0001) and protein levels were significantly inhibited. In conclusion, as a competitive endogenous RNA of miR-661. AL133467.1 promotes the expression of TOB2, thereby inhibiting the proliferation and invasion of breast cancer cells.

Long non-coding RNA (lncRNA), a kind of RNA with a length over 200 nt, plays an important role in the regulation of epigenetics. As for the lack of coding Open Reading Frame (ORF), low sequence conservation and lack of known protein domains, it is considered that lncRNA is not able to encode proteins. With the rapid development and application of advanced technologies such as mass spectrometry, RNA sequencing and ribosomal analysis, lncRNA has been detected to contain sORFs that can be bound to ribosomes. Similar to mRNA, lncRNA is also transcribed by RNA polymerase II, therefore, lncRNA is highly likely to be translated. At present, small peptides encoded by lncRNA have been successfully detected by some online tools and experimental techniques. Because there are shortcomings of the current experimental techniques, such as the difficulty of detection of small molecular weight peptides and antibody synthesis of small peptides, only a small number of lncRNA encoding small peptides have been identified compared with large scale lncRNA. The small peptide encoded by LncRNA plays an important role in the organism, such as participating in embryonic development, myogenesis, tumorigenesis and progression. In particular, small peptides encoded by lncRNA with abnormal expression in tumors are expected to become small molecule drugs, drug targets and biomarkers for tumor treatment, for which the attractive application prospects are shown. The commonly used online tools and experimental techniques for predicting and verifying small peptides encoded by lncRNA are briefly introduced in the article, and the functions of small peptides encoded by lncRNA are summarized, for which the application prospects in tumors are discussed. Meanwhile, the current research challenges faced by lncRNA coding small peptides are also analyzed, which could provide a reference for a better understanding and study of small peptides encoded by lncRNA.

Long non-coding RNAs (lncRNAs) are a class of nucleotide transcripts over 200 nt in length. Studies have shown that lncRNA can regulate physiological processes such as cell differentiation, immune response and apoptosis. LncRNA plays an important role in the occurrence and development of a variety of metabolic diseases and cancers. In the above physiological or pathological processes, lncRNA usually acts as a regulator of gene expression and causes the abnormal expression of downstream target genes. However, how the differential expression of lncRNA itself is regulated in these diseases remains unclear. Like other genes, lncRNA expression is regulated at the DNA level, transcriptional level and post-transcriptional level. The regulation of DNA level is the most important link in gene expression regulation. Studies have shown that the loss of chromosome 8 fragment and DNA copy number variation are common gene events in tumors. LncRNA genes are included in these DNA fragments with deletion or abnormal increase in copy number; In addition to DNA fragment loss and copy number variation, promoter region methylation, histone modification and DNA spatial conformation change are also included. At the transcriptional level, binding and activation of promoters by transcription factors is the most common mechanism. Post-transcriptional regulation mainly refers to the regulation of the stability of lncRNAs. Studies have found that microRNA (miRNA) can bind to the untranslated region (UTR) of the 3′ UTR end of lncRNAs to reduce the level of lncRNAs. In addition, the m⁶A methylation modification of lncRNAs also affects the stability and function of lncRNAs. In this paper, the regulatory mechanisms of pre-transcriptional level, transcriptional level and post-transcriptional level would be elaborated in order to provide some reference for the subsequent studies on the regulatory mechanisms of lncRNA.

Exosomes are small vesicles with double lipid membranes secreted by cells into the extracellular space and body fluids. Exosomes contain genetic materials, proteins, lipids and so on, and thus unveil a novel mechanism of intercellular communication. CircRNAs, which function as “microRNA sponges”, are emerging regulator for gene expression. CircRNAs exist in a variety of cells, thereby widely affect the life process of cells through different regulatory networks at the pre- and post-transcriptional levels. The critical role of exosomal circRNAs in the physiological and pathological processes has also attracted increasing attention. Aging process is driven by various contributing factors, which inevitably impairs tissue function and increases susceptibility to disease and death. It is demonstrated that the presence and progressive accumulation of senescent cells contributes to overall organism aging. Senescent cells aggregated in aging tissues have been considered as a causal factor for aging-related disorders. Recent studies have suggested that exosomal circRNAs might act as the senescence-associated secretory phenotype (SASP)of senescent cells and play an important role in the aging process and the occurrence of aging-related diseases. This review introduced the occurrence of exosomal circRNAs in detail, and summarized the research advances of exosomal circRNAs in aging and aging-related diseases. This study may provide references for the further research and clinical application of exosomal circRNAs.

Exosomes are cell-secreted nano-scale vesicles which are rich in a variety of biologically active substances and function as the important mediators in cell-to-cell communication. Long non-coding RNAs (lncRNAs) have impacts on the tumorigenesis and tumor progression from various aspects, and are specifically sorted into exosomes. Tumor microenvironment (TME), an internal environment composed of tumor cells, non-tumor cells (such as endothelial cells, immune cells, fibroblasts, etc.) and extracellular matrix, plays a vital role in the tumorigenesis and tumor progression. Tumor cells secrete large amounts of exosomes into TME. This article summarizes the roles of tumor-derived exosomal lncRNAs in TME from the perspective of how they regulate receptor cells, such as promoting tumor metastasis, drug resistance, cell metabolic reprogramming, tumor stemness, epithelial to mesenchymal transition (EMT), tumor angiogenesis and lymphangiogenesis, and immunosuppression. An in-depth understanding of the role of tumor-derived exosomal lncRNA in TME will help to provide potential new clinical biomarkers and therapeutic targets for cancer.

G-quadruplex (G4) is a non-canonical nucleic acid secondary structure composed of guanine-rich DNA or RNA sequences. In the past few decades, researchers have focused on the G-rich sequences in gene promoter region, UTR, telomere and other common gene functional regions, and explored the relationship between their structure and function. In recent years, due to the in-depth study of non-coding RNA in diseases, G-rich sequences in non-coding RNA, especially miRNA, have attracted more attention. G-rich sequence has been involved in the whole physiological process of miRNA, from pri-miRNA, pre-miRNA to mature miRNA: the dynamic balance formed between the G-quadruplex and the RNA stem-loop structure affect the maturation process of primary and precursor miRNA, causing the change of mature miRNA as well as the complementary pairing between miRNA and mRNA. This review focuses on reviewing the dynamic changes between G4 and hairpin structure, expounds the role of G-rich sequence in pri-miRNA, pre-miRNA, mature miRNA and mRNA. The important role of G-quadruplex in the maturation and function of miRNA was also discussed. It was concluded that the changes of external regulatory factors such as ionic conditions (K+, Mg2+, K++Mg2+, Li++Mg2+, etc) and G-quadruplex ligand molecules (destabilizer TMPyP4 , etc) could regulate the balance between G-quadruplex and stem-loop structure, thus regulating the corresponding functions of miRNA, providing ideas and directions for the study of G-quadruplex function and regulation.

Circular RNAs (circRNAs) are a class of non-coding RNAs that form closed rings in structure. They contain a high content in eukaryotic transcripts, and are characterized by richness, stability, high conservatism and tissue specificity. In recent years, it has been gradually revealed that circRNA can bind to some miRNAs or proteins and participate in the regulatory mechanisms of biogenesis and molecular functions, including the regulation of miRNAs molecular sponge, protein translation, gene transcription and RNA splicing. With the application of high-throughput sequencing and bioinformatics, circRNA has gradually become a new research hotspot in the field of non-coding RNA due to its special properties. The latest research evidence shows that circRNA plays a key role in the occurrence and development of tumors, and is inextricably linked with cell proliferation, apoptosis, angiogenesis, and metastasis, indicating that targeting circRNA will be an attractive treatment strategies and potential biomarkers. In this paper, the characteristics and mechanism of circRNA were briefly described, the mechanism of action and regulation of circRNAs in human tumors were summarized, and the strategies and development prospects of circRNA in tumor research were further discussed, so that circRNA could play an important role in early diagnosis, precise treatment and prognosis prediction of tumors.

G-quadruplex (G4) is a non-canonical nucleic acid secondary structure composed of guanine-rich DNA or RNA sequences. In the past few decades, researchers have focused on the G-rich sequences in gene promoter region, UTR, telomere and other common gene functional regions, to understand the relationship between their structure and function. In recent years, due to the in-depth study of non-coding RNA in diseases, G-rich sequences in non-coding RNA, especially miRNA, have attracted more attention. G-rich sequence has been involved in all physiological processes of miRNA synthesis, from primary miRNA (pri-miRNA), precursor miRNA (pre-miRNA) to mature miRNA: the dynamic balance formed between the G-quadruplex and the RNA stem-loop structure affects the maturation process of primary and precursor miRNA, causing the change of mature miRNA and the complementary pairing between miRNA and mRNA. This review focused on the dynamic changes between G4 and hairpin structure, and expounded the role of G-rich sequence in pri-miRNA, pre-miRNA, mature miRNA and mRNA. The important role of G-quadruplex in the maturation and function of miRNA was also discussed. It was concluded that the changes of external regulatory factors such as ionic conditions (K⁺, Mg²⁺, K⁺+Mg²⁺, Li⁺+Mg²⁺, etc) and G-quadruplex ligand molecules (destabilizer TMPyP4, etc) could regulate the balance between G-quadruplex and stem-loop structure, thus modulating the functions of miRNA. This review may help providing ideas and directions for the study of G-quadruplex function and regulation.

Circular RNAs (circRNAs) are a class of non-coding RNAs that form closed rings in structure. They contain a high content in eukaryotic transcripts, and are characterized by richness, stability, high conservatism and tissue specificity. In recent years, it has been gradually revealed that circRNA can bind to some miRNAs or proteins and participate in the regulatory mechanisms of biogenesis and molecular functions, including the regulation of miRNAs molecular sponge, protein translation, gene transcription and RNA splicing. With the application of high-throughput sequencing and bioinformatics, circRNA has gradually become a new research hotspot in the field of non-coding RNA due to its special properties. The latest research evidence shows that circRNA plays a key role in the occurrence and development of tumors, and is inextricably linked with cell proliferation, apoptosis, angiogenesis, and metastasis, indicating that targeting circRNA will be attractive treatment strategies and potential biomarkers. In this paper, the characteristics and mechanism of circRNA were briefly described, the mechanism of action and regulation of circRNAs in human tumors were summarized, and the strategies and development prospects of circRNA in tumor research were further discussed. In sum, circRNA plays an important role in early diagnosis, precise treatment and prognosis prediction of tumors.

Circular RNA (circRNA) is a new type of non-coding RNA with closed circular structure, widely distributed in various tissues. Compared with traditional linear RNA, circRNA does not have 5′ and 3′ ends and will not be easily degraded by exonuclease. It can stably exist in a variety of body fluids and is evolutionarily conservative. It has become a key research object of clinical non-coding RNA. Malignant tumors have the characteristics of late detection, rapid progress, and easy recurrence. Currently, there is still a lack of effective treatment methods, and their morbidity and mortality have been high. Therefore, how to carry out early diagnosis, treatment intervention and prognosis evaluation is one of the focuses and hotspots of contemporary medical research. CDR1as is the most widely studied circRNA. It can regulate the expression of downstream genes through sponge microRNA (miRNA) or directly bind to RNA-binding protein (RBP) to activate related signal pathways, thereby promoting or inhibiting tumor progression, and even affecting tumor chemotherapy sensitivity; CDR1as mainly exists in the cytoplasm and can be released into the blood at the early stage of the disease. Therefore, CDR1as may become a biomarker for early diagnosis of malignant tumors or an ideal target for therapeutic intervention. Based on the characteristics and biological functions of circRNA, this article reviews the expression level, mechanism of action and related signal pathways of CDR1as in the occurrence and development of malignant tumors. At the same time, this article analyzes the current research status of CDR1as, preliminarily summarizes the problems it may face in clinical application in the future, and puts forward ideas and suggestions on the future research direction of CDR1as.

Circular RNA (circRNA) is a new type of non-coding RNA with closed circular structures that are widely distributed in various tissues. Compared with traditional linear RNA, circRNA does not have 5′ and 3′ ends and will not be easily degraded by exonuclease. It can stably exist in a variety of body fluids and is evolutionarily conserved. It has become a key research object of clinical non-coding RNA. Malignant tumors have the characteristics of late detection, rapid progression, and easy recurrence. Currently, effective treatment methods are lacking, and their morbidity and mortality have been high. Therefore, how to carry out early diagnosis, treatment intervention and prognosis evaluation is one of the research frontier of contemporary medical research. CDR1as is the most widely studied circRNA. It can regulate the expression of downstream genes through sponge microRNA (miRNA) or directly bind to RNA-binding proteins (RBPs) to activate related signaling pathways, thereby promoting or inhibiting tumor progression, and even affecting tumor chemotherapy sensitivity. CDR1as mainly exists in the cytoplasm and can be released into the blood at the early stage of the disease. Therefore, CDR1as may become a biomarker for early diagnosis of malignant tumors or an ideal target for therapeutic intervention. Focusing on the characteristics and biological functions of circRNA, this article reviews the expression level, mechanism of action and related signaling pathways of CDR1as in the occurrence and development of malignant tumors. At the same time, this article analyzes the current research status of CDR1as, preliminarily summarizes the problems it may face in clinical applications in the future, and puts forward ideas and suggestions on the future research direction of CDR1as.

Circular RNAs (circRNAs) are a novel class of long-chain non-coding RNAs. Preceding evidence has showed that circRNAs participate in the development and progression of various tumors. In the present study, we investigated the expression of circRNAs in 5 paired colorectal cancer (CRC) tissues and adjacent normal tissues with circRNA high-throughput sequencing. Totally 477 differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues, which included 252 significantly overexpressed circRNAs and 225 downregulated circRNAs. CircRNA plasmacytoma variant translocation 1 (circPVT1), the most up-regulated expression circRNA, was further confirmed by qRT-PCR in 150 colorectal cancer tissues and matched normal mucosae. Our data revealed that circPVT1 showed a significant up-regulation trend in CRC tissues compared with matched normal mucosae. Similarly, compared with normal colorectal mucosa cells, the expression of circPVT1 in colorectal cancer cell lines was significantly up-regulated (P<0.05). Functionally, silence with siRNA or overexpression of circPVT1 in colorectal cancer cells was applied to determine the biological functions of circPVT1, including cell proliferation, apoptosis, and cell cycle, etc. The results show that circPVT1 expression significantly attenuated apoptosis, induced replication and promoted proliferation of colorectal cancer cells in vitro. In summary, our findings indicate that circPVT1 plays an oncogenic role in CRC and might be a potential novel target for CRC therapy.

Corneal epithelial wound healing (CEWH) is vital for maintaining tissue integrity and transparency, but its detailed molecular mechanism is unclear. Previous our study has shown that the expression of miR-203 is dramatically down-regulated during CEWH. Such changes suggest that miR-203 is an important effector of CEWH. In this study, we confirmed down-regulation of miR-203 during CEWH in mice. In vitro experiments, we transfected miR-203 into human corneal epithelial cells (HCECs) to overexpress miR-203. The MTS method, EdU detection, flow cytometry, scratch tests and transwell experiments were used to detect changes in cell proliferation, cell cycle, and cell migration after transfection. As a result, it was found that miR-203 can inhibit the proliferation of HCECs (P＜0.01). The cell cycle at the G₁ phase of HCECs was up-regulated by 10.63% compared to the negative control group, and cell apoptosis was increased (P＜0.01). Scratch experiments and transwell experiments have confirmed that overexpression of miR-203 can inhibit the migration of HCECs. Bioinformatics prediction and Western blot identified that SRC (SRC proto-oncogene) was a target gene of miR-203. The proliferation rate of HCECs was slowed down when the expression of SRC was knocked down (P＜0.001). Compared with the negative control group, the G₁ phase of the SRC knockdown group was up-regulated by 17.19%, and the apoptosis rate was increased (P<0.01). Scratch experiments and transwell experiments also confirmed that reducing the expression of SRC can inhibit the migration of HCECs. This study shows that miR-203 may affect HCECs proliferation and migration by down-regulating the expression of SRC, which will provide novel insight regarding the role played by miR-203 in mediating CEWH and identify more selective drug targets for the treatment of patients with damaged corneas.

Melanoma is an aggressive cancer with a poor prognosis. Understanding the molecular mechanism and diagnostic markers of melanoma is extremely important for the prevention and treatment of melanoma. LncRNAs play an important role in the genesis and progression of tumors. LncRNA-177922 was highly expressed in B16-F10 melanoma, compared with normal melanocytes. The loss of mitogen-activated protein kinase 15 (MAPK15) affects tumor initiation and progression. Here, LncRNA-177922 was overexpressed in B16-F10 cells, and the results showed that the mRNA and protein of related-genes to melanogenesis, proliferation, and migration were significantly up-regulated (P<0.05), the mRNA levels and protein abundance of autophagy-related genes were down-regulated (P<0.05), and the PI3K/AKT/mTOR pathway was activated. Also, the phenotypes of cell proliferation, migration, and autophagy were further verified. The results suggested that LncRNA-177922 targeted MAPK15 in regulating the biological processes of B16-F10 cells such as melanogenesis, proliferation, migration, and autophagy through the cross-point extracellular regulated protein kinases (ERK), which might provide potential new therapeutic targets and diagnostic markers.

Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) that are more than 200 nucleotides in length, without protein-coding functions. More than 90% of the transcripts from the genome are ncRNA transcripts. LncRNAs have been determined to play unique roles in various biological processes with their specific structures and functions, and have emerged as a hot spot in gene-characteristics, function-identification, and biological process regulation. Previous work has confirmed that lncRNAs are involved in pathogenesis of clinical diseases, especially in tumorigenesis. In the post-genomics era, prevention, diagnosis and prognosis in certain diseases could be processed by detection on lncRNA expression alteration, phenotype changes and molecular mechanisms that are involved. Here, we defined lncRNAs, listed the strategies and methods of genetic identification, enumerated methods in spatial structure inspection and functional identification, and showed the classification of lncRNAs. Moreover, lncRNA participated in tumorigenesis. We took the most classic tumor suppressor p53 as an example, as p53-related lncRNAs are involved in colorectal cancer (CRC). We summarize the expression alterations, interaction molecules and signaling pathways of these lncRNAs Finally, the clinical application value of these lncRNAs are estimated. Collectively, lncRNAs may function as biomarkers, and will provide series of brand new, accurate and unique targets for diverse diseases including CRC.

ILF3 antisense RNA 1 (ILF3-AS1)，the antisense RNA of interleukin enhancer binding factor 3 (ILF3)，is a lncRNA located on chromosome 19p13-2. ILF3-AS1 played a key role in the occurrence and development of a variety of tumors, but its role in cervical cancer had not been explored yet. Therefore, we first used TCGA and GTEx database to conduct bioinformatics analysis. The results suggested that ILF3-AS1 was down-regulated in cervical cancer tissues (P<0.001) and was associated with a good prognosis (P=0.045). The qRT-PCR experiment showed that expression of ILF3-AS1 in cervical cancer tissues and SiHa, HeLa, CaSki cervical cancer cell lines was lower than that in control groups. Subsequently, overexpressing of ILF3-AS1 can significantly inhibit the cancer cell viability and stimulate apoptosis (P<0.001). Analysis using the Star Base v3.0 database suggested that ILF3-AS1 can target miR-130a-3p; while miR-130a-3p may target PTEN. The qRT-PCR test showed that the expression of miR-130a-3p in cervical cancer was significantly higher than that in normal cervical tissues (P<0.01). The results of the luciferase reporter assay showed that ILF3-AS1 can specifically bind to miR-130a-3p (P<0.01). After overexpression of ILF3-AS1 in HeLa cells, the expression of miR-130a-3p was significantly down-regulated (P<0.01). Co-transfection with pcDNA3-1-ILF3-AS1 and miR-130a-3p mimics, the inhibitory effect of LF3-AS1 on cell proliferation can partially be reversed (P<0.001). After HeLa cells overexpressed ILF3-AS1, the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) mRNA (P<0.001) and proteins (P<0.001) significantly increased; when miR-130a-3p mimics was simultaneously used in HeLa cell, the increased expression of PTEN mRNA (P<0.001) and proteins (P<0.001) was notably inhibited. In summary, ILF3-AS1 inhibited the proliferation of cervical cancer cells by sponging miR-130a-3p to regulate the expression of PTEN.

Although many microRNAs (miRNAs) are known to function as regulators of coat color and melanogenesis, the underlying molecular mechanisms of miR-100-5p governing melanogenesis were not completely known. The goal of this study was to determine the effect of miR-100-5p on melanogenesis in alpaca melanocytes. Fibroblast growth factor 21 (FGF21) is a predicted target gene of miR-100-5p and the luciferase reporter assay demonstrated that miR-100-5p regulates FGF21 by binding to its 3′ untranslated region (3′UTR). In this study, alpaca melanocytes were transfected with miR-100-5p, inhibitor and negative control plasmid. Results showed that miR-100-5p overexpression significantly decreased mRNA and protein expression of FGF21. Meanwhile, the ERK signal pathway was inhibited, with subsequent up-regulation of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2), which increased melanin production. The results suggest that miR-100-5p may regulate melanogenesis by targeting FGF21 via extracellular regulated MAP kinase (ERK) signaling pathway.