circHERC4_041 Inhibits the Fibrotic Phenotype of Cardiac Fibroblasts by Encoding Protein
10.13865/j.cnki.cjbmb.2025.02.1476
- VernacularTitle:circHERC4_041通过编码蛋白质抑制心肌成纤维细胞纤维化表型作用
- Author:
Yuan GAO
1
;
Chuan-Meng ZHOU
;
Hua-Yan WU
;
Ya WANG
;
Ru-Shi WU
;
Pei-Ying GUAN
;
Jun-Tao FANG
;
Jin-Dong XU
;
Yu-Peng LIU
;
Zhi-Qin HU
;
Zhi-Xin SHAN
Author Information
1. 南方医科大学附属广东省人民医院医学研究部,广州 510080
- Publication Type:Journal Article
- Keywords:
cardiac fibrosis;
circular RNA(circRNA);
circHERC4_041;
translation;
cardiac fibro-blast
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(3):393-403
- CountryChina
- Language:Chinese
-
Abstract:
A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.
