摘要
目的 探讨长链非编码RNA-小核仁RNA宿主基因3(lncRNA-Snhg3)在小鼠肝脏糖代谢途径中的作用及调节机制。方法 通过尾静脉注射腺病毒的方法在糖尿病模型db/db小鼠过表达Snhg3,检测小鼠葡萄糖耐量和丙酮酸耐量,采用RT-qPCR分析小鼠肝脏糖异生相关基因磷酸烯醇式丙酮酸羧激酶Pepck、葡萄糖-6-磷酸酶G6pc及Snhg3的临近基因应激诱导蛋白2(Sestrin2,Sesn2)的变化;运用双荧光素酶报告基因实验检测293T细胞中Snhg3对Sesn2编码基因的启动子活性的作用。结果 腺病毒过表达Snhg3改善db/db小鼠葡萄糖耐量和丙酮酸耐受性,抑制糖异生基因Pepck和G6pc的mRNA表达(P<0.05),促进了Sesn2的mRNA表达(P<0.01)。同时,在293T细胞中过表达Snhg3可明显促进Sesn2启动子活性(P<0.05)。结论 Snhg3通过促进Sestrin2的表达改善小鼠糖代谢稳态。
Objective To investigate the role of long non-coding RNA-small nucleolar RNA host gene 3(lncRNA-Snhg3)and its regulatory mechanism in the hepatic glucose metabolism of mice.Methods Adenovirus Snhg3 was over-expressed by the tail vein injection in db/db mice,and then glucose tolerance and pyruvate tolerance were measured.The mRNA expression of mouse liver gluconeogenesis-related genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pc)and stress-inducing protein 2(Sestrin2,Sesn2,a gene adjacent to Snhg3)were detected by RT-qPCR.The dual luciferase reporter assay was used to detect the effect of Snhg3 on the Sesn2 promoter activity in 293T cells.Results Snhg3 over-expression improved glucose tolerance and pyruvate tolerance in db/db mice.Snhg3 over-expression inhibited the mRNA of gluconeogenesis genes of Pepck(P<0.05)and G6pc(P<0.05),while promoted the mRNA of Sesn2(P<0.01).Meanwhile,Snhg3 over-expression promoted Sesn2 promoter activity in 293T cells(P<0.05).Conclusions Snhg3 improves glucose metabolism in mice by promoting Sestrin2 expression.
作者
张明龙
高明月
解相宏
郭泽宇
刘晓军
闫莉
ZHANG Minglong;GAO Mingyue;XIE Xianghong;GUO Zeyu;LIU Xiaojun;YAN Li(Department of Pathophysiology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China;Department of Biochemistry and Molecular Biology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China)
出处
《基础医学与临床》
2025年第6期714-719,共6页
Basic and Clinical Medicine
基金
国家重点研发计划(2022YFC2504002)。
关键词
小核仁RNA宿主基因3
肝脏糖异生
应激诱导蛋白2
small nucleolar RNA host gene 3(Snhg3)
hepatic gluconeogenesis
stress-inducing protein 2(Sestrin 2)
