MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma
MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma
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DOI：
10.1111/j.1742-4658.2011.08120.x
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发表时间：
2011-06-01
期刊：
影响因子：
5.4
通讯作者：
Tang, Hua
中科院分区：
文献类型：
--
作者：
Wu, Nannan;Liu, Xuyuan;Tang, Hua
MicroRNA是一类小的非编码RNA，在转录后水平上作为基因表达的关键调节因子发挥作用。最近，发现microRNA-373（miR-373）在睾丸生殖细胞肿瘤中作为癌基因发挥作用。我们的研究发现，miR-373在人肝癌组织中的表达高于癌旁正常组织，并通过调节G（1）-期和S-期的转换促进肝癌细胞系HepG 2和QGY-7703的增殖。通过使用荧光报告基因分析，将编码蛋白磷酸酶6催化亚基（PPP 6C）（一种细胞周期负调控因子）的基因鉴定为miR-373的直接靶基因。PPP 6C的mRNA和蛋白水平均与miR-373表达水平呈负相关。PPP 6C过表达可阻断miR-373对HepG 2细胞周期和细胞生长的调控。提示miR-373在HCC的发病机制中起重要作用，可能成为HCC新的生物标志物。我们的研究结果表明，miR-373可以通过靶向PPP 6C转录调控细胞周期进程，并促进肝癌细胞的体外生长活性。miR-373对PPP 6C的下调可能解释了miR-373的表达促进HCC细胞增殖的原因。
MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. Recently, microRNA-373 (miR-373) has been found to function as an oncogene in testicular germ cell tumors. In our study, we found that miR-373 is upregulated in human hepatocellular carcinoma (HCC) tissues as compared with adjacent normal tissues, and promotes the proliferation of the HCC cell lines HepG2 and QGY-7703 by regulating the transition between G(1)-phaseand S-phase. The gene encoding the protein phosphatase 6 catalytic subunit (PPP6C ), a negative cell cycle regulator, was identified as a direct target gene of miR-373 by use of a fluorescent reporter assay. The mRNA and protein levels of PPP6C were both inversely correlated with the miR-373 expression level. Overexpression of PPP6C abolished the regulation of cell cycle and cell growth exercised by miR-373 in HepG2 cells. These results indicate that miR-373 plays an important role in the pathogenesis of HCC, and may be a new biomarker in HCC. Our results demonstrate that miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR-373 may explain why the expression of miR-373 can promote HCC cell proliferation.