MicroRNA-127 Post-Transcriptionally Downregulates Sept7 and Suppresses Cell Growth in Hepatocellular Carcinoma Cells

MicroRNA-127 Post-Transcriptionally Downregulates Sept7 and Suppresses Cell Growth in Hepatocellular Carcinoma Cells
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DOI:
10.1159/000358717
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发表时间:
2014-01-01
影响因子:
--
通讯作者:
Jiao, Binghua
Jiao, Binghua
中科院分区:
医学1区
文献类型:
--
作者:
Zhou, Jiansheng;Lu, Shan;Jiao, Binghua

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背景/目的:肝细胞癌是世界上最常见的癌症之一。已经表明,microRNA,一类小的调节RNA,通过靶向调节多种生物过程(包括细胞分化、凋亡、代谢和增殖)的数百个基因的mRNA而与肿瘤发生相关。方法/结果:我们使用qRT-PCR分析了33例HCC和非癌组织中mir-127的表达水平。miR-127在69.7%的HCC组织中表达下调,但其表达水平与TNM分期、AFP水平和年龄无关。在体外,miR-127可将Huh 7阻滞在G2/M期,抑制Huh 7细胞增殖。在体内异种移植模型中,miR-127的过表达可以抑制Huh 7细胞的致瘤性。荧光素酶报告基因和蛋白质印迹结果证实miR-127通过靶向其3 ' UTR下调Sept 7表达。此外,在Huh 7细胞中,敲低Sept 7对细胞增殖具有与过表达miR-127相同的作用。结论:miR-127具有抑癌作用,可作为HCC诊断的潜在生物标志物。版权所有(C)2014 S. Karger AG,巴塞尔
Background/Aims: Hepatocellular carcinoma is one of the most common cancers worldwide. It has been suggested that microRNAs, a class of small regulatory RNAs, are associated with tumorigenesis by targeting the mRNAs of hundreds of genes that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism, and proliferation. Methods/Results: we analyzed the expression levels of mir-127 in 33 HCC and non-cancerous tissues using qRT-PCR. MiR-127 is downregulated in 69.7% of HCC tissues compared with adjacent normal tissues, but its expression level is not correlated with the TNM stage, AFP level, or age. In vitro, miR-127 can arrest Huh7 at the G2/M phase and inhibit Huh7 cell proliferation. In an in vivo xenograft model, the overexpression of miR-127 can inhibit Huh7 cell tumorigenicity. The luciferase reporter and western blot results confirm that miR-127 downregulates Sept7 expression by targeting its 3 ' UTR. Furthermore, the knockdown of Sept7 has the same effect on cell proliferation as the overexpression of miR-127 in Huh7 cells. Conclusion: miR-127 plays a tumor-suppressor role and can serve as a potential diagnostic biomarker for HCC. Copyright (C) 2014 S. Karger AG, Basel