Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, No.29, Xin Quan Road, Fuzhou 350001, China.
Carcinogenesis. 2011 Nov;32(11):1641-7. doi: 10.1093/carcin/bgr199. Epub 2011 Sep 1.
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.
微小 RNA（miRNAs）是小的非编码 RNA 分子，通常位于基因组断裂点区域，可作为人类癌症中的癌基因或肿瘤抑制基因发挥作用。我们之前的研究表明，定位于 17q11 染色体频繁扩增区域的 microRNA-423（miR-423）在肝细胞癌（HCC）中上调。然而，miR-423 在肝发生中的潜在功能和确切的机制作用仍不清楚。在这里，我们证明 miR-423 可显著促进 HCC 细胞中 G1/S 期的细胞生长和细胞周期进程。特别是，我们发现 miR-423-3p 有助于这些作用，而 miR-423-5p 则没有。进一步的研究表明，p21Cip1/Waf1 是 HCC 细胞中 miR-423 的下游靶标，因为 miR-423 直接与其 3'非翻译区结合，并降低 p21Cip1/Waf1 的信使 RNA 和蛋白水平。此外，强制表达 p21Cip1/Waf1 可消除 miR-423 对 HCC 细胞增殖和细胞周期进程的诱导作用。这些发现表明，miR-423 通过抑制肿瘤抑制因子 p21Cip1/Waf1 的表达在肝发生中发挥促生长作用。本研究的结果将 miR-423 定义为 HCC 中的一种新的致癌 miRNA。
