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微小RNA-195-5p通过靶向PHF19在肝细胞癌中发挥抑癌基因的作用。

MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma.

作者信息

Xu Hui, Hu Yan-Wei, Zhao Jia-Yi, Hu Xiu-Mei, Li Shu-Fen, Wang Yan-Chao, Gao Ji-Juan, Sha Yan-Hua, Kang Chun-Min, Lin Li, Huang Chuan, Zhao Jing-Jing, Zheng Lei, Wang Qian

机构信息

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Oncol Rep. 2015 Jul;34(1):175-82. doi: 10.3892/or.2015.3957. Epub 2015 May 7.

Abstract

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.

摘要

肝细胞癌(HCC)是全球第五大常见恶性肿瘤。PHD指蛋白19(PHF19)编码一种多梳蛋白家族(PcG)成员,该蛋白通过维持许多发育调控基因的抑制性转录状态发挥作用。此外,已有研究表明miR - 195在HCC的分子病因学中起重要作用;然而,PHF19对HCC的影响及可能机制尚不清楚,且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的致癌活性及机制。我们的结果表明,基于生物信息学分析和荧光素酶报告基因检测结果,PHF19是hsa - miR - 195 - 5p的潜在靶点。用hsa - miR - 195 - 5p模拟物转染后,PHF19表达下调。此外,我们证明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hsa - miR - 195 - 5p的过表达降低了PHF19的表达,导致体外肝癌细胞侵袭、迁移和增殖受到抑制。此外,PHF19显著促进了异种移植肿瘤的生长,而hsa - miR - 195 - 5p显著抑制了裸鼠体内异种移植肿瘤的生长。这些结果提供了证据,表明PHF19促进HCC,且受抑癌基因miR - 195 - 5p调控。

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