suppresses autophagic flux N6-methyladenosine demethylation of mRNA in acute pancreatitis.

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 of in 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. and were knocked down to study the function in AP. A mA RNA binding protein immunoprecipitation assay was used to study how the m6A modification of mRNA 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 of and upregulation of and demonstrated that autophagy was impaired in AP. The expression of was upregulated in AP. Inhibition of increased the expression of and decreased the expression of the inflammatory factors, and . Furthermore, was upregulated in AP. Knockdown of downregulated expression and restored decreased autophagic flux in AP. Notably, the bioinformatic analysis revealed 23 potential mA modification sites on mRNA. The mA modification of mRNA was significantly decreased in AP. Knockdown of increased the modification of mRNA, which confirmed that upregulated expression in a mA-dependent manner.

CONCLUSION

inhibits autophagic flux through mA demethylation of mRNA in AP, thereby aggravating the severity of the disease.