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miR-21 靶向肿瘤抑制因子 RhoB,调节结直肠癌细胞的增殖、侵袭和凋亡。

miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells.

机构信息

Department of Medical Oncology/Laboratory of Signal Transduction and Molecular Targeted Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

出版信息

FEBS Lett. 2011 Oct 3;585(19):2998-3005. doi: 10.1016/j.febslet.2011.08.014. Epub 2011 Aug 26.

Abstract

It has become increasingly clear that microRNAs play an important role in many human diseases including cancer. Here, we show that expression of miR-21 in HEK293 and several colorectal cancer cells was found inversely correlated with ras homolog gene family, member B (RhoB) expression. miR-21 expression significantly suppressed RhoB 3' UTR luciferase-reporter activity, but the inhibitory effect was lost when the putative target sites were mutated. Exogenous miR-21 over-expression mimicked the effect of RhoB knockdown in promoting proliferation and invasion and inhibiting apoptosis, whereas anti-miR-21 or RhoB expression yielded opposite effects, in colorectal cancer cells. These results suggest that miR-21 is a regulator of RhoB expression and RhoB could be a useful target in exploring the potential therapeutic benefits of miR-21 mediated tumor cell behaviors in colorectal cancer.

摘要

越来越多的证据表明, microRNAs 在许多人类疾病中发挥着重要作用,包括癌症。在这里,我们发现 miR-21 在 HEK293 和几种结直肠癌细胞中的表达与 ras 同源基因家族成员 B(RhoB)的表达呈负相关。miR-21 的表达显著抑制 RhoB 3'UTR 荧光素酶报告基因活性,但当假定的靶位点发生突变时,抑制作用消失。外源性 miR-21 过表达模拟了 RhoB 敲低在促进增殖、侵袭和抑制凋亡方面的作用,而抗 miR-21 或 RhoB 表达则产生相反的效果,在结直肠癌细胞中。这些结果表明,miR-21 是 RhoB 表达的调节剂,RhoB 可能是探索 miR-21 介导的结直肠癌细胞行为潜在治疗益处的有用靶点。

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