MicroRNA-423 promotes cell growth and regulates G1/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma
MicroRNA-423 promotes cell growth and regulates G1/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma
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DOI：
10.1093/carcin/bgr199
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发表时间：
2011-11-01
期刊：
影响因子：
4.7
通讯作者：
He, Xianghuo
中科院分区：
文献类型：
--
作者：
Lin, Jun;Huang, Shenglin;He, Xianghuo
MicroRNAs （miRNAs）是一种小的非编码RNA分子，通常位于基因组断点区域，在人类癌症中可以作为致癌基因或肿瘤抑制基因。我们之前的研究表明，microRNA-423 （miR-423）定位于染色体17q11频繁扩增的区域，在肝细胞癌（HCC）中表达上调。然而，miR-423在肝癌发生中的潜在功能和确切机制作用尚不清楚。在这里，我们证明了miR-423在HCC细胞的G(1)/S转变中显著促进细胞生长和细胞周期进程。特别是，我们发现miR-423-3p有助于这些影响，而miR-423-5p则没有。进一步的研究表明，p21Cip1/Waf1是HCC细胞中miR-423的下游靶点，因为miR-423直接结合到其3'非翻译区并降低p21Cip1/Waf1的信使RNA和蛋白质水平。此外，p21Cip1/Waf1的强制表达消除了mir -423诱导的对HCC细胞增殖和细胞周期进展的影响。这些发现表明，miR-423通过抑制肿瘤抑制因子p21Cip1/Waf1的表达，在肝癌发生过程中发挥促生长作用。本研究结果将miR-423定义为HCC中一种新的致癌miRNA。
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.