suppresses autophagic fluxN6-methyladenosine demethylation ofmRNA in acute pancreatitis.

Abstract

BACKGROUND: Increasing evidence has demonstrated that N6-methyladenosine (mA) RNA modification plays an essential role in a wide range of pathological conditions. Impaired autophagy is a critical hallmark of acute pancreatitis (AP). AIM: To explore the role of the mA modification ofin the regulation of autophagy in AP. METHODS: The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells (MPC-83), and the results were confirmed by the levels of amylase and inflammatory factors. Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.andwere knocked down to study the function in AP. A mA RNA binding protein immunoprecipitation assay was used to study how the m6A modification ofmRNA is regulated by. RESULTS: The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established. The downregulation ofand upregulation ofanddemonstrated that autophagy was impaired in AP. The expression ofwas upregulated in AP. Inhibition ofincreased the expression ofand decreased the expression of the inflammatory factors,and. Furthermore,was upregulated in AP. Knockdown ofdownregulatedexpression and restored decreased autophagic flux in AP. Notably, the bioinformatic analysis revealed 23 potential mA modification sites onmRNA. The mA modification ofmRNA was significantly decreased in AP. Knockdown ofincreased the modification ofmRNA, which confirmed thatupregulatedexpression in a mA-dependent manner. CONCLUSION: inhibits autophagic flux through mA demethylation ofmRNA in AP, thereby aggravating the severity of the disease.