Suppr超能文献

miRNA - 770 - 5p在2型糖尿病患者中表达上调,且敲低miRNA - 770 - 5p可通过靶向BAG5表达来保护胰腺β细胞功能。

miRNA-770-5p expression is upregulated in patients with type 2 diabetes and miRNA-770-5p knockdown protects pancreatic β-cell function via targeting BAG5 expression.

作者信息

Wang Min, Wei Jilou, Ji Ting, Zang Kui

机构信息

Department of Critical Care Medicine, The First Affiliated Huai'an People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

出版信息

Exp Ther Med. 2021 Jul;22(1):664. doi: 10.3892/etm.2021.10096. Epub 2021 Apr 22.

Abstract

MicroRNA (miR)-770-5p expression is increased in patients with type 2 diabetes mellitus (T2DM) compared with healthy controls; however, the roles and molecular mechanism underlying miR-770-5p in T2DM are not completely understood. In the present study, the reverse transcription-quantitative PCR (RT-qPCR) results indicated that miR-770-5p expression was significantly increased and Bcl-2 associated athanogene 5 (BAG5) expression was significantly decreased in the serum of patients with T2DM compared with healthy volunteers. TargetScan and a dual luciferase reporter gene system were used to predict and verify BAG5 as a target gene of miR-770-5p. Additionally, the RT-qPCR results demonstrated that miR-770-5p expression was significantly increased and BAG5 expression was significantly decreased in uric acid (UA)-treated Min6 cells compared with control cells. Min6 cells were transfected with miR-770-5p inhibitor and BAG5-small interfering (si)RNA to alter expression levels. The results indicated that miR-770-5p negatively regulated BAG5. The effect of miR-770-5p knockdown on UA-induced pancreatic β-cell damage and dysfunction was subsequently assessed. Min6 cells were transfected with miR-770-5p inhibitor or miR-770-5p inhibitor + BAG5-siRNA for 48 h, followed by treatment with or without 5 mg/dl UA for 24 h. Cell viability, apoptosis, apoptosis-related factor expression levels and insulin secretion were assessed. The results demonstrated that UA treatment significantly reduced cell viability, increased cell apoptosis and reduced insulin secretion in Min6 cells compared with the control group. miR-770-5p inhibitor significantly attenuated UA-induced injury and dysfunction of Min6 cells, whereas BAG5 knockdown abolished the protective effects of miR-770-5p inhibitor on UA-damaged Min6 cells. In conclusion, miR-770-5p was highly expressed in the serum of patients with T2DM compared with healthy volunteers. In UA-treated pancreatic β-cells, compared with the inhibitor control group, miR-770-5p knockdown regulated the expression of apoptosis-related genes, increased cell viability, inhibited cell apoptosis and increased insulin secretion by targeting BAG5. Therefore, the present study suggested that miR-770-5p inhibitor may serve a protective role in T2DM.

摘要

与健康对照组相比,2型糖尿病(T2DM)患者体内的微小RNA(miR)-770-5p表达增加;然而,miR-770-5p在T2DM中的作用及分子机制尚未完全明确。在本研究中,逆转录定量PCR(RT-qPCR)结果表明,与健康志愿者相比,T2DM患者血清中miR-770-5p表达显著增加,而Bcl-2相关抗凋亡基因5(BAG5)表达显著降低。利用TargetScan和双荧光素酶报告基因系统预测并验证BAG5为miR-770-5p的靶基因。此外,RT-qPCR结果显示,与对照细胞相比,尿酸(UA)处理的Min6细胞中miR-770-5p表达显著增加,BAG5表达显著降低。用miR-770-5p抑制剂和BAG5小干扰(si)RNA转染Min6细胞以改变其表达水平。结果表明,miR-770-5p对BAG5起负向调控作用。随后评估了敲低miR-770-5p对UA诱导的胰腺β细胞损伤和功能障碍的影响。用miR-770-5p抑制剂或miR-770-5p抑制剂+BAG5-siRNA转染Min6细胞48小时,随后用或不用5mg/dl UA处理24小时。评估细胞活力、凋亡、凋亡相关因子表达水平及胰岛素分泌。结果表明,与对照组相比,UA处理显著降低了Min6细胞的活力,增加了细胞凋亡,并减少了胰岛素分泌。miR-770-5p抑制剂显著减轻了UA诱导的Min6细胞损伤和功能障碍,而敲低BAG5则消除了miR-770-5p抑制剂对UA损伤的Min6细胞的保护作用。总之,与健康志愿者相比,miR-770-5p在T2DM患者血清中高表达。在UA处理的胰腺β细胞中,与抑制剂对照组相比,敲低miR-770-5p通过靶向BAG5调控凋亡相关基因的表达,增加细胞活力,抑制细胞凋亡并增加胰岛素分泌。因此,本研究表明miR-770-5p抑制剂可能在T2DM中发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5c/8112148/82855fb48991/etm-22-01-10096-g00.jpg

相似文献

3
miR-142-5p regulates lipopolysaccharide-induced bovine epithelial cell proliferation and apoptosis via targeting BAG5.
Exp Ther Med. 2021 Dec;22(6):1425. doi: 10.3892/etm.2021.10860. Epub 2021 Oct 11.
4
Resveratrol improves uric acid-induced pancreatic β-cells injury and dysfunction through regulation of miR-126.
Biomed Pharmacother. 2018 Jun;102:1120-1126. doi: 10.1016/j.biopha.2018.03.172. Epub 2018 Apr 5.
7
miR-149-5p protects against high glucose-induced pancreatic beta cell apoptosis via targeting the BH3-only protein BIM.
Exp Mol Pathol. 2019 Oct;110:104279. doi: 10.1016/j.yexmp.2019.104279. Epub 2019 Jun 28.
8
MicroRNA-18 promotes apoptosis of islet β-cells via targeting NAV1.
Exp Ther Med. 2019 Jul;18(1):389-396. doi: 10.3892/etm.2019.7527. Epub 2019 Apr 24.
10
Role of miR-139-5p in ectopic endometrial stromal cells and the underlying molecular mechanism.
Exp Ther Med. 2021 Nov;22(5):1251. doi: 10.3892/etm.2021.10686. Epub 2021 Sep 2.

本文引用的文献

1
MicroRNA-770-5p contributes to podocyte injury via targeting E2F3 in diabetic nephropathy.
Braz J Med Biol Res. 2020;53(9):e9360. doi: 10.1590/1414-431x20209360. Epub 2020 Jul 17.
6
miR-429 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by downregulation of TLN1.
Cancer Cell Int. 2019 Apr 30;19:115. doi: 10.1186/s12935-019-0831-0. eCollection 2019.
7
Islet inflammation in type 2 diabetes.
Semin Immunopathol. 2019 Jul;41(4):501-513. doi: 10.1007/s00281-019-00745-4. Epub 2019 Apr 15.
10
Role of microRNAs (miRNAs) in the pathophysiology of diabetes mellitus.
Panminerva Med. 2018 Mar;60(1):25-28. doi: 10.23736/S0031-0808.17.03382-1. Epub 2017 Nov 10.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验