Snhg3通过促进Sestrin2的表达改善小鼠糖代谢

doi:10.16352/j.issn.1001-6325.2025.06.0714

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (6): 714-719.doi: 10.16352/j.issn.1001-6325.2025.06.0714

Snhg3通过促进Sestrin2的表达改善小鼠糖代谢

张明龙^1,2, 高明月², 解相宏², 郭泽宇², 刘晓军², 闫莉^1*

中国医学科学院基础医学研究所北京协和医学院基础学院 1.病理生理学系; 2.生物化学与分子生物学系, 北京 100005

收稿日期:2025-02-27 修回日期:2025-03-21 出版日期:2025-06-05 发布日期:2025-05-26
通讯作者: ^*yanli@ibms.pumc.edu.cn
基金资助:
国家重点研发计划(2022YFC2504002)

Snhg3 improves glucose metabolism by promoting Sestrin2 expression in mice

ZHANG Minglong^{1, 2}, GAO Mingyue², XIE Xianghong², GUO Zeyu², LIU Xiaojun², YAN Li^1*

1. Department of Pathophysiology; 2. Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2025-02-27 Revised:2025-03-21 Online:2025-06-05 Published:2025-05-26

摘要/Abstract

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。

关键词: 小核仁RNA宿主基因3, 肝脏糖异生, 应激诱导蛋白2

Abstract: 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.

Key words: small nucleolar RNA host gene 3(Snhg3), hepatic gluconeogenesis, stress-inducing protein 2(Sestrin 2)

中图分类号:

R587.1

张明龙, 高明月, 解相宏, 郭泽宇, 刘晓军, 闫莉. Snhg3通过促进Sestrin2的表达改善小鼠糖代谢[J]. 基础医学与临床, 2025, 45(6): 714-719.

ZHANG Minglong, GAO Mingyue, XIE Xianghong, GUO Zeyu, LIU Xiaojun, YAN Li. Snhg3 improves glucose metabolism by promoting Sestrin2 expression in mice[J]. Basic & Clinical Medicine, 2025, 45(6): 714-719.

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Snhg3通过促进Sestrin2的表达改善小鼠糖代谢

Snhg3 improves glucose metabolism by promoting Sestrin2 expression in mice

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