MicroRNA-363-5p Targets THBS3 to Regulate the Mechanism of Myocardial Apoptosis under Angiotensin Ⅱ Induction
10.13241/j.cnki.pmb.2025.09.002
- VernacularTitle:MicroRNA-363-5p靶向THBS3在血管紧张素Ⅱ诱导下调控心肌凋亡机制的研究
- Author:
Xin-yi HAN
1
;
Hui-ting LIU
;
Zheng-yi SHAN
;
Xue-yan ZHOU
;
Peng ZHAO
Author Information
1. 青岛大学基础医学院 山东青岛 266000
- Publication Type:Journal Article
- Keywords:
microRNA-363-5p;
Endoplasmic reticulum stress;
Cardiomyocyte apoptosis;
Cctivated transcription factor 6;
Thrombospondin
- From:
Progress in Modern Biomedicine
2025;25(9):1452-1469
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of microRNA-363-5p targeted binding to THBS3 on angiotensin Ⅱ-induced apoptosis in cardiomyocytes and its molecular mechanism.Methods:A human-derived cardiomyocyte cell line(AC16)was used to establish an in vitro cardiomyocyte apoptosis model with angiotensin Ⅱ(AngⅡ),and a dual luciferase reporter assay was performed to detect the relationship between miR-363-5p and THBS3;apoptosis rate was detected by flow cytometry,and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was performed to detect the relative expression of microR-363-5p,ATF-6mRNA,THBS3mRNA expression;Western Blot to detect the relative expression of caspase-12,caspase-3,GRP78,Bax,Bcl-2.Results:(1)Compared with the control group,the relative expression level of miR-363-5p in AngⅡ group was significantly decreased.(2)Compared with Mir-inhibitor-NC and Mir-mimics-NC groups,the apoptosis rate of miR-inhibitor and miR-mimics groups was significantly increased and decreased,the relative expression level of Bax protein was significantly increased and decreased,and the relative expression level of Bcl-2 was decreased and increased.(3)miR-363-5p targeted binding to THBS3.(4)Compared with the THBS3-OENC group,the relative expression of Bax and caspase-3 proteins was significantly higher,the relative expression of Bcl-2 protein was significantly lower,and the apoptosis rate was higher in the THBS3-OE group.(5)Compared with the negative control group,the relative expression of Bax and caspase-3 proteins in the miR-mimcs+THBS3-OE group was significantly higher,the relative expression of Bcl-2 protein was significantly lower,the apoptosis rate was significantly higher,and the cell viability was significantly lower.(6)Compared with the miR-inhibitor group,the relative expression of GRP78 and caspase-12 was decreased in the miR-inhibitor-4-PBA group,and the apoptosis rate was significantly reduced.(7)Compared with the negative control group,the apoptosis rate was elevated in the ATF-6-OE group,and the relative expression of caspase-12 was significantly increased.(8)Compared with the negative control group,miR-inhibitor+ATF-6 siRNA group showed decreased apoptosis rate and decreased relative expression of caspase-12.Conclusions:MicroRNA-363-5p is able to target binding to THBS3 to regulate myocardial apoptosis,a process that may be mediated through the endoplasmic reticulum stress ATF-6 pathway.
