A-to-I RNA editing of miR-411 attenuates post-infarction cardiac fibrosis via dual targeting of TGFBR2 and CD44
10.12025/j.issn.1008-6358.2025.20250656
- VernacularTitle:A-to-I编辑的miR-411通过靶向TGFBR2和CD44减轻梗死后心脏纤维化
- Author:
Suling DING
1
;
Zhiwei ZHANG
2
;
Xiyang YANG
3
;
Dili SUN
3
;
Jianfu ZHU
3
;
Xiaowei ZHU
4
;
Xiangdong YANG
5
;
Junbo GE
5
Author Information
1. Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China;Key Laboratory of Viral Cardiovascular Diseases, National Health Commission, Shanghai 200032, China.
2. Reproductive Medicine Center, Zhongshan Hospital, Shanghai 200032, China.
3. Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China.
4. Department of Critical Care Medicine, Shanghai 200032, China.
5. Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China;Key Laboratory of Viral Cardiovascular Diseases, National Health Commission, Shanghai 200032, China;Department of Cardiology, Huizhou Third People’s Hospital, Huizhou 516002, Guangdong, China.
- Publication Type:Conferenceabstract
- Keywords:
RNA editing;
cardiac fibrosis;
typeⅡtransforming growth factor-beta receptor;
CD44
- From:
Chinese Journal of Clinical Medicine
2026;33(1):191-192
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.
