SNHG3 通过调控 ERK/p38 信号通路减轻心肌缺血再灌注损伤。

SNHG3/miR-330-5p/HSD11B1 Alleviates Myocardial Ischemia-reperfusion Injury by Regulating the ERK/p38 Signaling Pathway.

机构信息

Department of Cardiovascular medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, 563002, P.R. China.

出版信息

Protein Pept Lett. 2023;30(8):699-708. doi: 10.2174/0929866530666230721143705.

DOI:10.2174/0929866530666230721143705

PMID:37488754

Abstract

BACKGROUND

Studies have found that microRNAs (miRNAs) participate in the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). miR-330-5p alleviated cerebral IR injury and regulated myocardial damage. However, the mechanism of the effect of miR-330-5p on MIRI needs to be further studied.

OBJECTIVE

The study aimed to explore the role and mechanism of miR-330-5p in MIRI.

METHODS

The oxygen-glucose deprivation reperfusion (OGD/R) model was constructed in cardiomyocytes to simulate MIRI in vitro. QRT-PCR was used for the detection of gene expression. ELISA was used for evaluation of the levels of aldehyde dehydrogenase 2 family member (ALDH2), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA). Flow cytometry was used to evaluate apoptosis. Western blot was employed for protein determination. Bioinformatic analysis was performed for predicting the targets of miR-330-5p.

RESULTS

miR-330-5p was found to be down-regulated in MIRI-induced cardiomyocytes (Model group). miR-330-5p mimic enhanced ALDH2 activity, inhibited apoptosis, and suppressed 4-HNE and MDA of MIRI-induced cardiomyocytes. miR-330-5p inhibited ERK expression while increasing the p38 expression. Bioinformatic analysis showed hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) to be a target of miR-330-5p. HSD11B1 expression was inhibited by miR-330-5p mimic while increased by miR-330-5p inhibitor in MIRI-induced cardiomyocytes. HSD11B1 overexpression reversed the effect of miR-330-5p on ALDH2, 4-HNE, MDA, apoptosis, and ERK/p38 signaling pathway. Furthermore, lncRNA small nucleolar RNA host gene 3 (SNHG3) was the upstream lncRNA of miR-330-5p. SNHG3 decreased miR-330-5p expression and increased HSD11B1 expression.

CONCLUSION

SNHG3/miR-330-5p alleviated MIRI in vitro by targeting HSD11B1 to regulate the ERK/p38 signaling pathway.

摘要

背景

研究发现微小 RNA（miRNA）参与心肌缺血再灌注损伤（MIRI）的发病机制。miR-330-5p 减轻脑 IR 损伤并调节心肌损伤。然而，miR-330-5p 对 MIRI 的作用机制仍需进一步研究。

目的

本研究旨在探讨 miR-330-5p 在 MIRI 中的作用及机制。

方法

体外构建心肌细胞氧葡萄糖剥夺再灌注（OGD/R）模型模拟 MIRI。采用 QRT-PCR 检测基因表达。ELISA 法检测醛脱氢酶 2 家族成员（ALDH2）、4-羟基壬烯醛（4-HNE）和丙二醛（MDA）水平。流式细胞术检测细胞凋亡。Western blot 法检测蛋白表达。生物信息学分析预测 miR-330-5p 的靶基因。

结果

MIRI 诱导的心肌细胞（模型组）中 miR-330-5p 表达下调。miR-330-5p 模拟物增强 ALDH2 活性，抑制细胞凋亡，抑制 MIRI 诱导的心肌细胞 4-HNE 和 MDA。miR-330-5p 抑制 ERK 表达，增加 p38 表达。生物信息学分析显示羟类固醇 11-β 脱氢酶 1（HSD11B1）是 miR-330-5p 的靶基因。miR-330-5p 模拟物抑制 MIRI 诱导的心肌细胞中 HSD11B1 的表达，而 miR-330-5p 抑制剂则增加其表达。HSD11B1 过表达逆转了 miR-330-5p 对 ALDH2、4-HNE、MDA、细胞凋亡及 ERK/p38 信号通路的影响。此外，长链非编码 RNA 小核仁 RNA 宿主基因 3（SNHG3）是 miR-330-5p 的上游 lncRNA。SNHG3 降低 miR-330-5p 的表达，增加 HSD11B1 的表达。