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

Anorectal malformations 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 anorectal malformations. Elevated microRNA-141-3p expression inhibited Yin Yang 1 expression by binding its 3′-untranslated region, 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. Intra-amniotic microinjection of adeno-rno-microRNA-141-3p-sponge-green fluorescent protein in fetal rats with anorectal malformations 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 intra-amniotic injection of anti-microRNA-141-3p helped maintain homeostasis in the lumbosacral defecation center of anorectal malformations during embryogenesis.