Anti-miR-141-3p maintains homeostasis between autophagy and apoptosis by targeting Yy1 in the fetal lumbosacral defecation center of rats

Yue Li; Peiqi Liu; Yifan Yao; Weilin Wang; Huimin Jia; Yuzuo Bai; Zhengwei Yuan; Zhonghua Yang

doi:10.1016/j.omtn.2024.102163

Anti-miR-141-3p maintains homeostasis between autophagy and apoptosis by targeting Yy1 in the fetal lumbosacral defecation center of rats

Mol Ther Nucleic Acids. 2024 Mar 6;35(2):102163. doi: 10.1016/j.omtn.2024.102163. eCollection 2024 Jun 11.

Authors

Yue Li¹, Peiqi Liu¹, Yifan Yao¹, Weilin Wang¹, Huimin Jia¹, Yuzuo Bai¹, Zhengwei Yuan², Zhonghua Yang^{1

2}

Affiliations

¹ Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
² Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.

Abstract

Anorectal malformations (ARMs) are congenital diseases that lead to postoperative fecal incontinence, constipation, and soiling, despite improvements in surgery; however, their pathological mechanisms remain unclear. Here, we report the role of microRNA-141-3p in maintaining homeostasis between apoptosis and autophagy in the lumbosacral defecation center of fetal rats with ARMs. Elevated microRNA-141-3p expression inhibited YIN-YANG-1 expression by binding its 3' UTR, and repressed autophagy and triggered apoptosis simultaneously. Then, adenylate cyclase 3 was screened to be the downstream target gene of YIN-YANG-1 by chromatin immunoprecipitation sequencing experiments, and Yin Yang 1 could positively activate the transcription of adenylate cyclase 3 by directly interacting with the motif GAGATGG and ATGG in its promoter. Intraamniotic microinjection of adeno-rno-microRNA-141-3p-sponge-GFP in fetal rats with ARMs on embryonic day 15 restored apoptosis-autophagy homeostasis. These findings reveal that microRNA-141-3p upregulation impaired homeostasis between apoptosis and autophagy by inhibiting the YIN-YANG-1/adenylate cyclase 3 axis, and that intraamniotic injection of anti-microRNA-141-3p helped maintain homeostasis in the lumbosacral defecation center of ARMs during embryogenesis.

Keywords: Adcy3; MT: Oligonucleotides: Therapies and Applications; Yy1; anorectal malformations; intraamniotic injection; miR-141-3p.