Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a house-keeping glycolysis gene highly and constantly expressed in almost every tissue. So it is widely used as a relative reference to quantitate proteins, RNA and DNA. But in recent years, GAPDH has been questioned as an internal reference, especially in tumor and aging tissues. Extensive studies have indicated that GAPDH is up-regulated in tumors, and down-regulated in aging muscles. The high expression levels of GAPDH in tumors may be associated with tumor metastasis and proliferation. In this review, we cover the expression of GAPDH in tumor and aging tissues or cells, as well as the possible underlying mechanisms. We aim to provide a blueprint of GAPDH expression in these pathological and physiological processes, facilitating investigators to select a better internal reference in future molecular experiments.
郑琳, 郑慧玲, 刘新光. 管家基因GAPDH在肿瘤与衰老组织中作为内参应慎重[J]. 中国生物化学与分子生物学报, 2018, 34(4): 385-389.
ZHENG Lin, ZHENG Hui-Ling, LIU Xin-Guang. GAPDH Should Be Cautiously Used as an Internal Reference in Tumor and Aging Tissues. Chinese Journal of Biochemistry and Molecular Biol, 2018, 34(4): 385-389.
[1] Zhang JY, Zhang F, Hong CQ, et al. Critical protein GAPDH and its regulatory mechanisms in cancer cells[J]. Cancer Biol Med, 2015, 12(1):10-22
[2] Guo C, Liu S, Sun MZ. Novel insight into the role of GAPDH playing in tumor [J]. Clin Transl Oncol, 2013, 15(3):167-172
[3] Shafaee A, Dastyar DZ, Islamian JP, et al. Inhibition of tumor energy pathways for targeted esophagus cancer therapy[J]. Metabolism, 2015, 64(10):1193 -1198
[4] Lowe DA, Degens H, Chen KD, et al. Glyceraldehyde-3-phosphate dehydrogenase varies with age in glycolytic muscles of rats[J]. J Gerontol A Biol Sci Med Sci, 2000, 55(3):B160-B164
[5] Liu S, Sun Y, Jiang M, et al. Glyceraldehyde-3-phosphate dehydrogenase promotes liver tumorigenesis by modulating phosphoglycerate dehydrogenase[J]. Hepatology, 2017, 66(2): 631-645
[6] Jung M, Ramankulov A, Roigas J, et al. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR[J]. BMC Mol Biol, 2007, 8:47
[7] Zhao LM, Zheng ZX, Zhao X, et al. Optimization of reference genes for normalization of the quantitative polymerase chain reaction in tissue samples of gastric cancer[J]. Asian Pac J Cancer Prev, 2014, 15(14): 5815-5818
[8] Grillon E, Farion R, Reuveni M, et al. Spatial profiles of markers of glycolysis, mitochondria, and proton pumps in a rat glioma suggest coordinated programming for proliferation[J]. BMC Res Notes, 2015, 8: 207
[9] Chiche J, Pommier S, Beneteau M, et al. GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin's B lymphomas via NF-κB-dependent induction of HIF-1a[J]. Leukemia, 2015, 29(5):1163-1176
[10] Ramos D, Pellín-Carcelén A, Agustí J, et al. Deregulation of glyceraldehyde-3-phosphate dehydrogenase expression during tumor progression of human cutaneous melanoma[J]. Anticancer Res, 2015, 35(1):439-444
[11] Hao L, Zhou X, Liu S, et al. Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas[J]. Proteomics, 2015, 15(17): 3087 - 3100
[12] Mori R, Wang Q, Danenberg KD, et al. Both beta-actin and GAPDH are useful reference genes for normalization of quantitative RT-PCR in human FFPE tissue samples of prostate cancer[J]. Prostate, 2008, 68(14): 1555-1560
[13] Hansen CN, Ketabi Z, Rosenstierne MW, et al. Expression of CPEB, GAPDH and U6snRNA in cervical and ovarian tissue during cancer development[J]. APMIS, 2009, 117(1): 53-59
[14] Liu S, Zhu P, Zhang L, et al. Increased glyceraldehyde-3-phosphate dehydrogenase expression indicates higher survival rates in male patients with hepatitis B virus-accociated hepatocellular carcinoma and cirrhosis[J]. Exp Ther Med, 2015, 9(5):1597-1604
[15] Liu T, Li W, Lu W, et al. RBFOX3 Promotes Tumor Growth and Progression via hTERT Signaling and Predicts a Poor Prognosis in Hepatocellular Carcinoma[J]. Theranostics, 2017, 7(12): 3138-3154.
[16] 高丽,王玉霞,江文欣,等.转导hTERT基因致人牙髓干细胞永生化的研究[J]. 上海口腔医学(Gao L, Wang YX, Jiang WX, et al. Immortalization of human dental pulp stem cells caused by transferring hTERT gene[J]. Shanghai J Stomatol), 2015, 24(02):135-140
[17] Jaiswal RK, Kumar P, Sharma A, et al. Proteomic identification of proteins differentially expressed following overexpression of hTERT (human telomerase reverse transcriptase) in cancer cells[J]. PLoS One, 2017,12(7): e0181027
[18] Huang Y, Lin D,Taniguchi CM. Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe[J]? Sci China Life Sci, 2017, 60(10): 1114-1124
[19] Hinkelbein J, Jansen s, Iovino I,et al. Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum[J]. Int J Mol Sci, 2017, 18(9):1882
[20] Sharma NK, Sethy NK , Bhargava K. Comparative proteome analysis reveals differential regulation of glycolytic and antioxidant enzymes in cortex and hippocampus exposed to short-term hypobaric hypoxia[J]. J Proteomics, 2013,79: 277-298
[21] Rey MJD, Valin A,Usategui A,et al. Hif-1alpha Knockdown Reduces Glycolytic Metabolism and Induces Cell Death of Human Synovial Fibroblasts Under Normoxic Conditions[J]. Sci Rep, 2017, 7(1): 3644
[22] 何姝槿, 陈厚文,熊丽霞. MicroRNA对EMT的调节作用及其与肿瘤侵袭的关系[J]. 中国生物化学与分子生物学报(He SJ, Chen HW, Xiong LX. Effects of microRNA on tumor epithelial-mesenchymal transition[J]. Chin J Biochem Mol Biol), 2016, 32(11): 1197-1205
[23] 李洪利,尹崇高 ,李文通,等. 过表达Snail增强肺癌细胞A549的体外侵袭能力[J]. 中国生物化学与分子生物学报(Li HL, Yin CG, Li WT, et al. Overexpression of snail enhances the invasive capacity of human lung cancer cell A549 in culture[J]. Chin J Biochem Mol Biol), 2010,26(10):943-948
[24] Liu K, Tang Z, Huang A, et al.Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression[J]. Int J Oncol, 2017,50(1): 252-262
[25] Gannon J, Ohlendieck K. Subproteomic analysis of basic proteins in aged skeletal muscle following offgel pre-fractionation[J]. Mol Med Rep, 2012, 5(4):993-1000
[26] Vigelsø A, Dybboe R, Hansen CN, et al. GAPDH and β-actin protein decreases with aging, making Stain-Free technology a superior loading control in Western blotting of human skeletal muscle[J]. J Appl Physiol, 2015, 118(3):386-394
[27] Wyckelsma VL, Mckenna MJ, Levinger I, et al. Cell specific differences in the protein abundances of GAPDH and Na(+), K(+)-ATPase in skeletal muscle from aged individuals[J]. Exp Gerontol, 2016, 75:8-15
[28] Chen J, Rider DA, Ruan R. Identification of valid housekeeping genes and antioxidant enzyme gene expression change in the aging rat liver[J]. J Gerontol A Biol Sci Med Sci, 2006, 61(1): 20-27
[29] Slagboom PE, de Leeuw WJ, Vijg J. Messenger RNA levels and methylation patterns of GAPDH and beta-actin genes in rat liver, spleen and brain in relation to aging[J]. Mech Ageing Dev, 1990, 53(3): 243-257
[30] Zampieri M, Ciccarone F, Guastafierro T, et al. Validation of suitable internal control genes for expression studies in aging[J]. Mech Ageing Dev, 2010, 131(2): 89-95