Ubiquitin-conjugating enzyme E2C (UBE2C) is closely related to the proliferation of various tumor cells, but its relationship with the occurrence and development of lung cancer is not clear. The roles of UBE2C in cellular proliferation, cell senescence and migration of A549 lung cancer cells were elucidated by RT-PCR, Western blotting, immunofluorescence, SA-β-Gal cell senescence staining, cell scratch and Trans-well assays. Transient over-expression or targeted silencing of UBE2C by gene modification technique was used. The results showed that the expression of UBE2C in lung cancer cells was significantly higher than that in normal cells. The levels of UBE2C mRNA and protein were significantly increased by 3.5-fold or decreased by 0.5-fold in A549 cells after transient over-expression or silence of UBE2C, leading to significant promotion or inhibition of cell proliferation, thereby reducing or increasing the rate of apoptosis. In addition, over-expression of UBE2C significantly inhibited cell senescence, whereas silence of UBE2C promoted cell senescence. Moreover, UBE2C significantly affected the mRNA and protein expression of metastasis related genes E-cadherin and vimentin, and further modulated cell migration. This study provided information for the roles of UBE2C in the development and progression of lung cancer.
基金资助:烟台市科技发展计划 (No 2015ZH082)和山东省自然科学基金资助项目 (No ZR2018QH004, ZR2016HB55, ZR2017PH067)
通讯作者:
郭纪伟
E-mail: guojiwei0510@163.com
引用本文:
郭纪伟，武艳，金丹，杜静，宫凯凯，苗双，杨丽娟. 泛素偶联酶2C促进肺癌细胞增殖和迁移与抑制细胞衰老[J]. 中国生物化学与分子生物学报, 2018, 34(6): 649-658.
GUO Ji-Wei1) *， WU Yan，JIN Dan， DU Jing， GONG Kai-Kai，MIAO Shuang， YANG Li-Juan. UBE2C Promotes Proliferation and Migration of Lung Cancer Cells and Inhibits Cell Senescence. Chinese Journal of Biochemistry and Molecular Biol, 2018, 34(6): 649-658.
[1].参考文献(References)
[2]Siegel R, Naishadham D, Jemal A.Cancer statistics,2013[J].CA Cancer J Clin, 2013, 63(1):11-30
[3]Barton MK.Adjuvant chemotherapy benefits older and younger non-small cell lung cancer patients alike[J].CA Cancer J Clin, 2012, 62(5):279-280
[4]Ramalingam SS, Owonikoko TK, Khuri FR.Lung cancer: new biological insights and recent therapeutic advances[J].CA Cancer J Clin, 2011, 61(2):91-112
[5]汤锐明，邱惠思，黄岩，等.长链非编码 促进肺癌细胞增殖中国生物化学与分子生物学报[J].Chin J Biochem Mol Biol, 2017, 33(12):1274-1279
[6]陈刚, 王国栋, 王乃辉.通过靶向调节癌基因抑制非小细胞肺癌细胞的增殖中国生物化学与分子生物学报[J].Chin J Biochem Mol Biol, 2016, 32(2):184-190
[7]Hurria A, Kris MG.Management of lung cancer in older adults[J].CA Cancer J Clin, 2003, 53(6):325-341
[8]Greco FA, Hainsworth JD.Tumors of unknown origin[J].CA Cancer J Clin, 1992, 42(2):96-115
[9]Zhang Z, Liu P, Wang J, et al.Ubiquitin-conjugating enzyme E2C regulates apoptosis- dependent tumor progression of non-small cell lung cancer via ERK pathway[J].Med Oncol, 2015, 32(5):149-
[10]Summers MK, Pan B, Mukhyala K, et al.The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC[J].Mol Cell, 2008, 31(4):544-556
[11]Psyrri A, Kalogeras KT, Kronenwett R, et al.Prognostic significance of UBE2C mRNA expression in high-risk early breast cancerA Hellenic Cooperative Oncology Group (HeCOG) Study[J].Ann Oncol, 2012, 23(6):1422-1427
[12]Hao Z, Zhang H, Cowell J.Ubiquitin-conjugating enzyme UBE2C: molecular biology,role in tumorigenesis,and potential as a biomarker[J].Tumour Biol, 2012, 33(3):723-730
[13]Meyer HJ, Rape M.Processive ubiquitin chain formation by the anaphase-promoting complex[J].Semin Cell Dev Biol, 2011, 22(6):544-550
[14]Palumbo A Jr, Da Costa NM, De Martino M, et al.UBE2C is overexpressed in ESCC tissues and its abrogation attenuates the malignant phenotype of ESCC cell lines[J].Oncotarget, 2016, 7(40):65876-65887
[15]Ma R, Kang X, Zhang G, et al.High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma[J].Oncol Lett, 2016, 11(3):2300-2304
[16]van Ree JH, Jeganathan KB, Malureanu L, et al.Overexpression of the E2 ubiquitin- conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation[J].J Cell Biol, 2010, 188(1):83-100
[17]Wagner KW, Sapinoso LM, El-Rifai W, et al.Overexpression,genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin[J].Oncogene, 2004, 23(39):6621-6629
[18]Chen S, Chen Y, Hu C, et al.Association of clinicopathological features with UbcH10 expression in colorectal cancer[J].J Cancer Res Clin Oncol, 2010, 136(3):419-426
[19]Nath S, Banerjee T, Sen D, et al.A novel transcriptional role of spindle assembly checkpoint protein Cdc20 regulating the expression of mitotic ubiquitin carrier protein UbcH10[J].Cancer Res, 2011, 71(8 Suppl):3075-3075
[20] Xie C, Powell C, Yao M, et al.Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker [J]. Int J Biochem Cell Biol, 2014, 47: 113-117
[21]Hao Z, Zhang H, Cowell J.Ubiquitin-conjugating enzyme UBE2C: molecular biology,role in tumorigenesis,and potential as a biomarker[J].Tumour Biol, 2012, 33(3):723-730
