lncRNA SGO1-AS1通过调节SIRT1去乙酰化酶活性抑制细胞凋亡

LncRNA SGO1-AS1 Inhibited Apoptosis by Regulating the Deacetylase Activity of SIRT1

沉默信息调节因子1(silent information regulator 1, SIRT1)是NAD^+依赖的组蛋白去乙酰化酶,可以通过去乙酰化底物调节多种生物学功能。长链非编码RNA(long non-coding RNA, lncRNA)是一类新兴的基因表达调控子,可以影响多种生命进程。尽管如此,SIRT1与lncRNA之间的调控关系以及lncRNA在SIRT1介导的生物学功能中的作用还有待进一步阐明。因此,本研究旨在探讨SIRT1相关lncRNA SGO1-AS1在SIRT1介导的细胞凋亡中的作用及其分子机制。荧光定量PCR检测发现,过表达SIRT1可显著促进lncRNA SGO1-AS1的表达(P<0.05),反之沉默SIRT1则抑制SGO1-AS1的表达(P<0.001)。进一步利用Western印迹、胱天蛋白酶3/7活性检测和TUNEL实验发现,沉默SGO1-AS1可显著促进细胞凋亡(P<0.05),但并不明显影响DNA损伤修复。此外,Western印迹结果显示,SGO1-AS1还可显著促进SIRT1蛋白的去乙酰化酶活性。综上所述,lncRNA SGO1-AS1可以抑制细胞凋亡,且长链非编码RNA SGO1-AS1有可能与SIRT1形成正反馈调节环路,从而调控细胞凋亡。尽管如此,SGO1-AS1调节细胞凋亡分子机制依然有待深入研究。

Silent information regulator 1(SIRT1)is a NAD+-dependent histone deacetylase,which is involved in a variety of cellular functions through deacetylation of substrates.Long noncoding RNAs(lncRNAs)have emerged as key regulators for gene expression in multiple levels,and thus are involved in various biological processes.Nonetheless,the regulatory relationship between SIRT1 and lncRNA,and the effect of lncRNA on SIRT1-mediated functions are yet to be elucidated.This study aims to explore the effect and underlying mechanism of lncRNA SGO1-AS1 on SIRT1-mediated apoptosis.The data of qPCR showed that overexpression of SIRT1 significantly enhanced the expression of lncRNA SGO1-AS1(P<0.05),and silencing of SIRT1 dramatically inhibited the expression of SGO1-AS1(P<0.001),indicating that the expression of SIRT1 was positively correlated with the expression of SGO1-AS1.Moreover,the results of Western blotting,Caspase3/7 activity and TUNEL assays unveiled that knock-down of SGO1-AS1 promoted apoptosis(P<0.05),but had no significant effect on DNA damage repair.In addition,the results of Western blotting showed that SGO1-AS1 evidently enhanced the deacetylase of SIRT1.In sum,the present study provides evidence that lncRNA SGO1-AS1 may form a positive feedback loop with SIRT1,and suppress apoptosis;nonetheless,the underlying molecular mechanism of the effect of SGO1-AS1 on apoptosis still requires further investigation.