MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1
MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1
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DOI：
10.1016/j.biopha.2017.05.092
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发表时间：
2017-08-01
影响因子：
7.5
通讯作者：
Zhang, Jianjun
中科院分区：
文献类型：
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作者：
Li, Yuanhang;Bai, Weijun;Zhang, Jianjun
目的：目的：探讨miR-200 c-5 p/MAD 2L 1轴在人肝癌细胞增殖和转移中的生物学作用。通过双荧光素酶报告基因系统验证了miR-200 c-5 p与MAD 2L 1的相互作用。进行转染以操纵miR-200 c-5 p和MAD 2L 1在HCCLM 3细胞中的表达。结果：与正常组织相比，HCC组织和细胞中miR-200 c-5 p表达明显降低，而MAD 2L 1表达明显增高。miR-200 c-5 p和MAD 2L 1的异常表达与肿瘤分期、邻近器官侵袭和预后相关。通过双荧光素酶报告测定证实miR-200 c-5 p和MAD 2L 1之间的直接靶向关系。上调miR-200 c-5 p可下调MAD 2L 1的表达，抑制肝癌细胞的增殖、迁移、侵袭，并诱导肝癌细胞凋亡和细胞周期阻滞。结论：补充miR-200 c-5 p可抑制肝癌细胞的增殖、迁移和侵袭，其机制可能与抑制MAD 2L 1有关。miR-200 c-5 p可作为HCC患者的预后指标和有希望的治疗靶点。(C)2017年由Elsevier Masson SAS出版。
Objective: To explore the biological functions of miR-200c-5p/MAD2L1 axis on the proliferation and metastasis of human hepatocellular carcinoma (HCC) cells.Methods: The expression levels of miR-200c-5p and MAD2L1 in HCC tissues, adjacent tissues as well as HCC cell lines were detected by RT-qPCR or Western blot. The interaction between miR-200c-5p and MAD2L1 was verified by dual luciferase reporter gene system. Transfection was performed to manipulate the expression of miR-200c-5p and MAD2L1 in HCCLM3 cells. Colony formation, MTT, wound healing and Transwell assays were applied to measure the cell proliferation, migration and invasion of HCC, besides, flow cytometry analysis was also conducted to evaluate HCC cell cycle and apoptosis.Results: Low expression of miR-200c-5p and remarkable overexpression of MAD2L1 was uncovered in HCC tissues and cells compared with the normal. The aberrant expression of miR-200c-5p and MAD2L1 was correlated with tumor stage, adjacent organ invasion and prognosis. Direct target relationship between miR-200c-5p and MAD2L1 was confirmed by dual luciferase reporting assay. Up-regulation of miR-200c-5p downregulated MAD2L1 and suppressed the proliferation, migration, invasion and induced apoptosis and cell cycle arrest of HCC cells. Moreover, MAD2L1 promoted HCC cell viabilities and cotransfection of MAD2L1 restored the anti-tumor effects of miR-200c-5p overexpression.Conclusion: Replenishing of miR-200c-5p inhibited the proliferation, migration and invasion of HCC cells by suppressing MAD2L1. MiR-200c-5p can serve as a prognostic indicator and a promising therapeutic target for HCC patients. (C) 2017 Published by Elsevier Masson SAS.