SIRT5 promotes cell proliferation and invasion in hepatocellular carcinoma by targeting E2F1
SIRT5 promotes cell proliferation and invasion in hepatocellular carcinoma by targeting E2F1
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DOI：
10.3892/mmr.2017.7875
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发表时间：
2018-01-01
影响因子：
3.4
通讯作者：
Jian, Zhixiang
中科院分区：
文献类型：
--
作者：
Chang, Liang;Xi, Liang;Jian, Zhixiang
Sirtuin 5(SIRT5)是依赖NAD(+)的III类蛋白去乙酰基酶的成员。虽然已知SIRT5去乙酰化并激活小鼠肝脏线粒体中的尿酸氧化酶，但SIRT5在肝细胞癌(HCC)增殖中的作用机制仍未完全阐明。本研究探讨SIRT5在肝细胞癌中的表达及其功能意义，并探讨其相关机制。研究发现，SIRT5在肝癌组织和细胞系中表达上调，SIRT5的高表达表明总体生存较差。采用逆转录定量聚合酶链式反应分析、Western印迹分析、染色质免疫沉淀分析、荧光素酶报告基因、增殖和Transwell检测等方法，探讨SIRT5在人肝癌细胞增殖和侵袭调控中的作用。在功能上，SIRT5的抑制显著抑制了肝癌细胞的增殖和侵袭，而SIRT5的过表达促进了肝癌细胞的增殖和侵袭。E2F转录因子1(E2F1)是SIRT5的一个新的靶基因。此外，SIRT5基因敲除可诱导E2F1的表达，而肝癌细胞中E2F1基因的敲除部分逆转了SIRT5促进细胞增殖和侵袭的作用。总而言之，这些数据提供了第一个证据，就我们所知，SIRT5基因在肝癌的发生中具有重要的调节作用，并可能作为一种新的潜在的肝癌治疗靶点。
Sirtuin 5 (SIRT5) is a member of the NAD(+)-dependent class III protein deacetylases. Although it is known that SIRT5 deacetylates and activates urate oxidase in the liver mitochondria of mice, the mechanism of SIRT5 in the proliferation of hepatocellular carcinoma (HCC) remains to be fully elucidated. The present study investigated the expression and functional significance of SIRT5 in HCC, and examined the relevant mechanism. SIRT5 was found to be upregulated in HCC tissues and cell lines, and the higher expression of SIRT5 indicated poorer overall survival. Reverse transcription-quantitative polymerase chain reaction analysis, western blot analysis, chromatin immunoprecipitation analysis, and luciferase reporter gene, proliferation and Transwell assays were performed to elucidate the function of SIRT5 in the regulation of cell proliferation and invasion in human HCC. Functionally, it was observed that the inhibition of SIRT5 significantly suppressed HCC cell proliferation and invasion, whereas the overexpression of SIRT5 promoted HCC cell proliferation and invasion in vitro. E2F transcription factor 1 (E2F1) was identified as a novel target gene of SIRT5. In addition, the knockdown of SIRT5 induced the expression of E2F1, and the knockdown of E2F1 in HCC cells partially reversed the effect of SIRT5 in promoting cell proliferation and invasion. Collectively, these data provide the first evidence, to the best of our knowledge, that the SIRT5 gene has an important regulatory role in liver carcinogenesis, and may function as a novel potential therapeutic target for HCC.