Uncovering new MicroRNAs linked to acute pancreatitis: zeroing in on the protective effect.

BACKGROUND

The microRNA expression profile in the bodily fluids of individuals with acute pancreatitis (AP) undergoes considerable alterations; nevertheless, the precise mechanism requires more elucidation.

METHODS

A dataset of 2083 human blood microRNAs (miRNAs) was obtained from the miRNA expression quantitative loci data. The genome-wide association study data for AP was obtained from the FinnGen Consortium. The causal association between miRNA and susceptibility to AP was evaluated using the Mendelian randomization (MR) method. Receiver operating characteristic (ROC) curve analyses were implemented to assess the miRNA's clinical usefulness. The GSE188819 and GSE249349 datasets were analyzed to determine changes in cell subset amounts and differentially expressed genes during the advancement and regression of AP mice. We assessed the inhibitory impact of miR-27b-3p and miR-193a-5p overexpression on AR42J cell and RAW 264.7 cell inflammation using western blot.

RESULTS

Following a thorough process of genetic variation selection, MR analysis, and sensitivity analysis, we identified 66 miRNAs with suggestive causality to AP susceptibility. We conducted ROC curve analysis on 66 variables, identifying 6 miRNAs that have the potential to diagnose AP. Six and twelve cell subsets were identified from the GSE249349 and GSE188819 datasets, respectively. In the inflammatory advancement stage, the percentage of acinar cells in the AP group decreased relative to the control group samples. In the inflammatory regression phase, the percentage of monocytes in the AP (96 h) group decreased relative to the AP (12 h) group. In vitro, experiments have found that the overexpression of miR-27b-3p and miR-193a-5p in RAW 264.7 cells AR42J cells significantly inhibited the protein expression of p-P65.

CONCLUSION

Our research identified novel miRNAs associated with the pathogenesis of AP. In vitro experiments have confirmed that miR-27b-3p and miR-193a-5p can inhibit the inflammatory response in RAW 264.7 cells and AR42J cells.