@article{APS11608,
author = {Jin-feng Su and Tao Ou and Xiao-yao Liu and Xue-min Su and Ya Wang and Yi-hong Wen and Yuan Gao and Ruo-han Li and Lu-fang Huang and Chuan-meng Zhou and Heng-li Zhao and Jie-ning Zhu and Ning Ma and Xi-long Zheng and Yu-peng Liu and Jin-dong Xu and Hui Li and Xian-hong Fang and Zhi-xin Shan},
title = {S1UTRSP5, a short restructured RNA from SLIT1 3′UTR, mitigates mouse cardiac remodeling via enhancing SlRT1 activity},
journal = {Acta Pharmacologica Sinica},
volume = {47},
number = {9},
year = {2026},
keywords = {},
abstract = {The 3′ untranslated regions (3′UTRs) have been known to regulate mRNA location, stability, and translation. 3′UTR length regulation is involved in the pathogenesis of cardiac dysfunction; however, more about the roles of 3′UTRs in cardiac remodeling remains elusive. In this study, we found slit guidance ligand 1 (SLIT1) 3′UTR with 3074 nt in length, which was 10-fold higher than SLIT1 coding sequence (CDS), was significantly decreased in the myocardium of patients with heart failure (HF) (n = 40) in comparison with healthy organ donors (n=17). We revealed that SLIT1 3′UTR and the 1526 nt fragment of SLIT1 3′UTR (FS1UTR) mainly and specifically combined miR-34a-5p, and improved cardiac remodeling through the miR-34a-5p/SIRT1 axis independently of Slit1 expression. Furthermore, a 260 nt restructured RNA derived from FS1UTR, S1UTRSP5, which contains 5 binding sites of miR-34a-5p seed sequence, alleviated cardiac remodeling in vitro and in vivo. We demonstrated that S1UTRSP5 blocked the function of miR-34a-5p and activated the SIRT1-PGC-1α-Nrf2 axis in cardiomyocytes, and promoted the SIRT1/Smad3 signal in cardiac fibroblasts and the SIRT1-eNOS-VEGFA axis in endothelial cells, collectively contributing to the amelioration of cardiac remodeling. These results provide new insights into the development of S1UTRSP5 as a novel inhibitor of miR-34a-5p for cardiac remodeling and HF.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11608}
}