MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma
MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma
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DOI：
10.3892/or.2015.3957
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发表时间：
2015-07-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Qian
中科院分区：
文献类型：
--
作者：
Xu, Hui;Hu, Yan-Wei;Wang, Qian
肝细胞癌（HCC）是全球第五大最常见的恶性肿瘤。PHD指蛋白19 （PHF19）编码多梳蛋白群（polycomb group, PcG）的一个成员，其功能是维持许多发育调节基因的抑制转录状态。此外，研究表明miR-195在HCC的分子病因学中起着重要作用；然而，PHF19在HCC中的作用和可能的机制尚不清楚，PHF19与miR-195之间的关联很少被提及。在本研究中，我们在体内和体外研究了PHF19对HCC的致癌活性和机制。我们的研究结果表明，基于生物信息学分析和荧光素酶报告试验的结果，PHF19是hsa-miR-195-5p的潜在靶标。转染hsa-miR-195-5p模拟物后，PHF19下调。此外，我们证明了PHF19的过表达促进了肝癌细胞在体外的迁移、侵袭和增殖。相反，肝癌细胞中过表达hsa-miR-195-5p可降低PHF19的表达，从而抑制肝癌细胞在体外的侵袭、迁移和增殖。此外，PHF19显著促进异种移植肿瘤的生长，而hsa-miR-195-5p显著抑制裸鼠异种移植肿瘤的生长。这些结果提供了PHF19促进HCC并受肿瘤抑制因子miR-195-5p调节的证据。
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. PHD finger protein 19 (PHF19) encodes a member of the polycomb group (PcG) of proteins that functions by maintaining the repressive transcriptional states of many developmental regulatory genes. In addition, it has been shown that miR-195 plays an important role in the molecular etiology of HCC; however, the effect and possible mechanism of PHF19 on HCC is unclear, and the association between PHF19 and miR-195 has seldom been addressed. In the present study, we investigated the carcinogenic activity and mechanism of PHF19 on HCC in vivo and in vitro. Our results showed that PHF19 is a potential target of hsa-miR-195-5p based on a bioinformatic analysis and results of a luciferase reporter assay. PHF19 was downregulated after transfection with hsa-miR-195-5p mimics. Moreover, we demonstrated that overexpression of PHF19 promoted hepatoma cell migration, invasion and proliferation in vitro. In contrast, overexpression of hsa-miR-195-5p in hepatoma cells reduced PHF19 expression, leading to suppression of hepatoma cell invasion, migration and proliferation in vitro. In addition, PHF19 markedly promoted the growth of xenograft tumors, while hsa-miR-195-5p markedly suppressed the growth of xenograft tumors in nude mice. These results provide evidence that PHF19 promotes HCC and is regulated by the tumor-suppressor, miR-195-5p.