miR-145-5p靶向MEST抑制胃癌上皮细胞增殖侵袭转移的研究

摘要/Abstract

摘要： 目的探究miR-145-5p、MEST在胃癌上皮细胞的调控机制。方法生信分析miR-145-5p及MEST的表达情况、两者相关性以及靶向位点;利用qRT-PCR和Western blot检测miR-145-5p及MEST的表达;双荧光素酶实验检测miR-145-5p和MEST的靶向关系;采用细胞增殖实验、克隆形成实验、划痕实验以及Transwell实验检测胃癌上皮细胞的增殖、转移和侵袭能力。结果相比正常胃上皮细胞,胃癌上皮细胞中的miR-145-5p低表达,而MEST高表达;miR-145-5p和MEST之间存在靶向关系;过表达miR-145-5p能减弱MEST对癌细胞增殖、转移和侵袭的促进作用。结论 miR-145-5p在胃癌上皮细胞中低表达,MEST在胃癌上皮细胞中高表达;miR-145-5p可以通过靶向下调MEST,从而抑制胃癌细胞的增殖、转移和侵袭能力。

关键词: miR-145-5p, MEST, 胃癌, 增殖, 侵袭, 转移

Abstract: Objective To explore the regulatory mechanism of miR-145-5p and MEST in gastric cancer epithelial cells. Methods The expression, correlation and target sites of miR-145-5p and MEST were analyzed. qRT-PCR and Western blot were used to detect the expression of miR-145-5p and MEST. The dual luciferase experiment was used to detect targeting relationship between miR-145-5p and MEST. The cell proliferation experiment, clone formation experiment, scratch experiment and Transwell experiment were used to detect the proliferation, metastasis and invasion ability of gastric cancer epithelial cells. Results Compared with normal gastric epithelial cells, the expression of miR-145-5p in gastric cancer epithelial cells was low, while the expression of MEST was high. There was a targeting relationship between miR-145-5p and MEST, and the overexpression of miR-145-5p could weaken the effect of MEST on cancer cell proliferation, metastasis and invasion. Conclusion miR-145-5p is low expressed in gastric cancer epithelial cells, and MEST is high expressed in gastric cancer epithelial cells; miR-145-5p can target down-regulation of MEST, thereby inhibiting the proliferation, metastasis and invasion of gastric cancer cells.

Key words: miR-145-5p, MEST, gastric cancer, proliferation, invasion, metastasis

中图分类号:

R735.2

杨爱峰, 侯鹏飞. miR-145-5p靶向MEST抑制胃癌上皮细胞增殖侵袭转移的研究[J]. 承德医学院学报, 2020, 37(6): 451-455.

YANG Ai-feng, HOU Peng-fei. miR-145-5p Targeting MEST Inhibits the Proliferation, Invasion and Metastasis of Gastric Cancer Epithelial Cells[J]. Journal of Chengde Medical University, 2020, 37(6): 451-455.

参考文献

[1] Choi YJ, Kim N.Gastric cancer and family history[J]. Korean J Intern Med, 2016, 31(6): 1042-1053.
[2] Sridevi K Pokala, Chao Z, Zhengjia C, et al.Incidence, Survival, and Predictors of Lymph Node Involvement in Early-Stage Gastric Signet Ring Cell Carcinoma in the US[J]. J Gastrointest Surg, 2018, 22(4): 569-577.
[3] Ventura A, Jacks T.MicroRNAs and cancer: short RNAs go a long way[J]. Cell, 2009, 136(4) :586-591.
[4] Lu J, Getz G, Miska EA, et al.MicroRNA expression profiles classify human cancers[J]. Nature, 2005, 435(7034): 834-838.
[5] Michael MZ, SM OC, van Holst Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia[J]. Mol Cancer Res, 2003, 1(12): 882-891.
[6] Xu Q, Liu LZ, Qian X, et al.MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis[J]. Nucleic Acids Res, 2012, 40(2): 761-774.
[7] Spizzo R, Nicoloso MS, Lupini L, et al.miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells[J]. Cell Death Differ, 2010, 17(2): 246-254.
[8] Zaman MS, Chen Y, Deng G, et al.The functional significance of microRNA-145 in prostate cancer[J]. Br J Cancer, 2010, 103(2): 256-264.
[9] Zhang Y, Wen X, Hu XL, et al.Downregulation of miR-145-5p correlates with poor prognosis in gastric cancer[J]. Eur Rev Med Pharmacol Sci, 2016, 20(14): 3026-3030.
[10] Zhou T, Chen S, Mao X. miR-145-5p affects the differentiation of gastric cancer by targeting KLF5 directly[J]. J Cell Physiol, 2019, 234(5): 7634-7644.
[11] Nakanishi H, Suda T, Katoh M, et al.Loss of imprinting of PEG1/MEST in lung cancer cell lines[J]. Oncol Rep, 2004, 12(6): 1273-1278.
[12] Vidal AC, Henry NM, Murphy SK, et al.PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer[J]. Clin Transl Oncol, 2014, 16(3): 266-272.
[13] Yoshino H, Seki N, Itesako T, et al.Aberrant expression of microRNAs in bladder cancer[J]. Nat Rev Urol, 2013, 10(7): 396-404.
[14] Wei H, Wen-Ming C, Jun-Bo J.Plasma miR-145 as a novel biomarker for the diagnosis and radiosensitivity prediction of human cervical cancer[J]. J Int Med Res, 2017, 45(3): 1054-1060.
[15] Lu QC, Shan S, Li YY, et al.Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up-regulating MTDH via sponging miR-145-5p[J]. FASEB J, 2018, 32(7): 3957-3967.
[16] Tabrizi M, Khalili M, Vasei M, et al.Evaluating the miR-302b and miR-145 expression in formalin-fixed paraffin-embedded samples of esophageal squamous cell carcinoma[J]. Arch Iran Med, 2015, 18(3): 173-178.