miR-202 通过转录后下调 LRP6 抑制人肝癌细胞增殖。
miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally.
机构信息
Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, PR China.
Department of Oncology Nanfang Hosptial, Southern Medical University, Guangzhou 510515, PR China.
出版信息
FEBS Lett. 2014 May 21;588(10):1913-20. doi: 10.1016/j.febslet.2014.03.030. Epub 2014 Apr 3.
MicroRNAs have emerged as important regulators of carcinogenesis. In the current study, we observed that microRNA-202 (miR-202) is downregulated in hepatocellular carcinoma (HCC) cells and tissues, indicating a significant correlation between miR-202 expression and HCC progression. Overexpression of miR-202 in HCC cells suppressed cell proliferation and tumorigenicity, while downregulation of miR-202 enhanced the cells' proliferative capacity. Furthermore, we identified low-density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-202. miR-202 suppresses the expression of LRP6 by binding to the 3'-untranslated region (UTR) of its mRNA. Finally, we found that silencing the expression of LRP6 is the essential biological function of miR-202 during HCC cell proliferation. Collectively, our findings reveal that miR-202 is a potential tumor suppressive miRNA that participates in carcinogenesis of human HCC by suppressing LRP6 expression.
微小 RNA 已成为癌症发生的重要调节因子。在本研究中，我们观察到微小 RNA-202（miR-202）在肝癌（HCC）细胞和组织中下调，表明 miR-202 表达与 HCC 进展之间存在显著相关性。在 HCC 细胞中过表达 miR-202 抑制细胞增殖和致瘤性，而下调 miR-202 增强了细胞的增殖能力。此外，我们确定了低密度脂蛋白受体相关蛋白 6（LRP6）是 miR-202 的直接靶标。miR-202 通过结合其 mRNA 的 3'-非翻译区（UTR）来抑制 LRP6 的表达。最后，我们发现沉默 LRP6 的表达是 miR-202 在 HCC 细胞增殖过程中的重要生物学功能。总之，我们的研究结果表明，miR-202 是一种潜在的肿瘤抑制性 miRNA，通过抑制 LRP6 的表达参与人类 HCC 的致癌作用。
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