Carcinogenesis 2011 Nov;32 (11): 1641-7. [IF:5.402]
MicroRNA-423 promotes cell growth and regulates G1/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma.
Lin J , Huang S , Wu S , Ding J , Zhao Y , Liang L , Tian Q , Zha R , Zhan R , He X .
Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, No.29, Xin Quan Road, Fuzhou 350001, China.
福建医科大学附属协和医院血液科，福建省血液病研究所
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that are often located in genomic breakpoint regions and can act as oncogenes or tumor suppressor genes in human cancer. Our previous study showed that microRNA-423 (miR-423), which localized to the frequently amplified region of chromosome 17q11, was upregulated in hepatocellular carcinoma (HCC). However, the potential functions and exact mechanistic roles of miR-423 in hepatic carcinogenesis remain unknown. Here, we demonstrated that miR-423 significantly promotes cell growth and cell cycle progression at the G(1)/S transition in HCC cells. In particular, we found that miR-423-3p contributes to these effects, whereas miR-423-5p does not. Further studies revealed that p21Cip1/Waf1 is a downstream target of miR-423 in HCC cells, as miR-423 bound directly to its 3' untranslated region and reduced both the messenger RNA and protein levels of p21Cip1/Waf1. Moreover, enforced expression of p21Cip1/Waf1 abrogated miR-423-induced effects on HCC cell proliferation and cell cycle progression. These findings indicate that miR-423 exerts growth-promoting effects in hepatic carcinogenesis through the suppression of tumor suppressor p21Cip1/Waf1 expression. The results of this study define miR-423 as a new oncogenic miRNA in HCC.
摘要
MicroRNAs(miRNAs)是没有编码的小RNA分子，通常位于基因组断点部位，在人类癌症中可以作为致癌或肿瘤抑制基因。我们以前的研究表明,常常局限于17q11上的放大部位的microRNA-423 (miR-423)在肝细胞癌中上调。然而,miR-423在肝癌形成中的潜在功能和准确机械作用仍然不清楚。在这里,我们证实肝癌细胞miR- 423显著促进细胞生长及细胞G(1)/S转换周期进程。特别是,我们发现miR - 423- 3p有助于这些效应,而miR- 423 -5p没有。进一步的研究显示,肝癌细胞中p21Cip1 / Waf1是miR- 423下调的目标,因为miR-423直接限制他的3'非翻译部位，不仅减少信使RNA水平和而且减少蛋白质p21Cip1 / Waf1水平。此外,p21Cip1 / Waf1的表达的增强取消了miR-423在肝癌细胞增殖、细胞周期进程中的诱导影响。这些研究结果表明:在肝癌形成中， miR– 423通过肿瘤抑制器p21Cip1/ Waf1的表达来发挥促进生长的效应。这项研究的结果确定肝癌中miR- 423作为一种新型的致癌miRNA。
