Hepatitis C virus core protein impairs metabolic disorder of liver cell via HOTAIR-Sirt1 signalling.
Hepatitis C virus core protein impairs metabolic disorder of liver cell via HOTAIR-Sirt1 signalling.
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DOI：
10.1042/bsr20160088
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发表时间：
2016-07
影响因子：
4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li ZQ;Gu XY;Hu JX;Ping Y;Li H;Yan JY;Li J;Sun R;Yu ZJ;Zhang Y
有研究表明，丙型肝炎病毒核心蛋白与肝细胞代谢紊乱有关。然而，确切的机制仍不清楚。本研究旨在探讨丙型肝炎病毒核心蛋白对肝细胞代谢的影响以及长非编码(Lnc)RNA在这一过程中的可能作用。用定量RT-PCR方法检测丙型肝炎病毒核心蛋白对LncRNAs表达的影响。HVC核心蛋白和LncRNA HOTAIR的操作是为了评价它们之间的相互作用对细胞代谢相关基因表达和细胞代谢的影响。用Western blotting和qRT-PCR检测Sirt1的下游信号。我们的数据表明，抑制HOTAIR可以消除丙型肝炎病毒核心蛋白诱导的Sirt1减少以及糖和脂代谢相关基因的差异表达。细胞内ROS水平和NAD/NADH比值的恢复也有利于肝细胞代谢的动态平衡。通过对HOTAIR的操作，我们得出结论：HOTAIR通过影响其启动子甲基化来负性调节Sirt1的表达。此外，Sirt1的过表达逆转了pcDNA-HOTAIR诱导的糖和脂代谢相关基因的表达。我们的研究表明，丙型肝炎病毒核心蛋白通过HOTAIR-Sirt1信号通路导致肝细胞糖脂代谢紊乱。
It has been suggested that Hepatitis C virus (HCV) core protein is associated with metabolic disorders of liver cell. However, the precise mechanism is still unclear. The aim of the present study was to explore the impact of HCV core protein on hepatocyte metabolism by HepG2 and the possible involvement of long non-coding (lnc) RNAs in this process. The effect of HCV core protein on lncRNAs expression was examined with quantitative RT-PCR (qRT-PCR). Manipulation of HVC core protein and lncRNA HOTAIR was to evaluate the role of interaction between them on cell metabolism-related gene expression and cellular metabolism. The potential downstream Sirt1 signal was examined by western blotting and qRT-PCR. Our data suggested that suppression of HOTAIR abrogates HCV core protein-induced reduction in Sirt1 and differential expression of glucose- and lipid-metabolism-related genes. Also it benefits for metabolic homoeostasis of hepatocyte indicated by restoration of cellular reactive oxygen species (ROS) level and NAD/NADH ratio. By manipulation of HOTAIR, we concluded that HOTAIR negatively regulates Sirt1 expression through affecting its promotor methylation. Moreover, overexpression of Sirt1 reverses pcDNA-HOTAIR-induced glucose- and lipid-metabolism-related gene expression. Our study suggests that HCV core protein causes dysfunction of glucose and lipid metabolism in liver cells through HOTAIR-Sirt1 signalling pathway.