miR-19a correlates with poor prognosis of clear cell renal cell carcinoma patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression
miR-19a correlates with poor prognosis of clear cell renal cell carcinoma patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression
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miR-19a通过促进细胞增殖和抑制PTEN/SMAD4表达与透明细胞肾细胞癌患者的不良预后相关
DOI：
10.3892/ijo.2016.3746
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发表时间：
2016-12-01
影响因子：
5.2
通讯作者：
Liu, Tonghua
中科院分区：
文献类型：
--
作者：
Ma, Qiang;Peng, Zhiqiang;Liu, Tonghua
据报道，MicroRNAs （miRNAs）参与透明细胞肾细胞癌（ccRCC）的发展。然而，关于mirna在ccRCC中的研究还远未完成。本研究发现了可能作为ccRCC潜在的新型预后标志物的mirna，并分析了其可能的机制。我们发现miR-19a通过促进细胞增殖和抑制PTEN/SMAD4表达与ccRCC患者预后不良相关。微阵列筛选结果和TCGA KIRC数据集分析均显示miR-19a在ccRCC组织中显著上调，进一步TCGA数据分析发现miR-19a上调水平与ccRCC患者T期晚期和预后不良密切相关。与临床观察一致，miR-19a过表达显著促进体外ccRCC细胞增殖。为了进一步探讨miR-19a与ccRCC细胞增殖及预后不良相关的机制，我们对ccRCC患者中miR-19a的靶基因进行了基因集富集分析（GSEA）。结果表明miR-19a的关键靶基因包括SMAD4和PTEN。在ccRCC组织中，SMAD4和PTEN的表达水平与miR-19a的表达水平呈负相关，说明miR-19a抑制了ccRCC患者中SMAD4和PTEN的表达。miR-19a过表达在体外显著抑制SMAD4和PTEN的表达，进一步验证了SMAD4和PTEN是miR-19a在ccRCC细胞中的靶基因。我们的研究结果阐明了miR-19a的肿瘤促进作用，并确立了miR-19a作为ccRCC潜在的新型预后标志物。
MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found that miR-19a correlated with poor prognosis of ccRCC patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression. Both the microarray screening result and TCGA KIRC dataset analysis showed that miR-19a was significantly upregulated in ccRCC tissues, and further analysis of TCGA data revealed that the upregulated level of miR-19a was strongly associated with advanced T stage and poor prognosis of ccRCC patients. Consistent with clinical observations, miR-19a overexpression significantly promoted ccRCC cell proliferation in vitro. To further explore the mechanism by which miR-19a correlated with cell proliferation and poor prognosis of ccRCC, we performed gene set enrichment analysis (GSEA) for target genes of miR-19a in ccRCC patients. Result indicated that the key target genes of miR-19a included SMAD4 and PTEN. In ccRCC tissues, expression levels of SMAD4 and PTEN were negatively correlated with expression level of miR-19a, revealing that miR-19a suppressed the expression of SMAD4 and PTEN in ccRCC patients. miR-19a overexpression significantly suppressed the expression of SMAD4 and PTEN in vitro, further verifying that SMAD4 and PTEN were the target genes of miR-19a in ccRCC cells. Our results elucidated the tumor promoting role of miR-19a and established miR-19a as a potential novel prognostic marker for ccRCC.