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Uncovering new MicroRNAs linked to acute pancreatitis: zeroing in on the protective effect
Changcheng Zhao1, Shanshan Jia1, Hang Yu1
1Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
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.
Insights
This study identifies novel microRNAs (miRNAs) linked to acute pancreatitis (AP) susceptibility. Specific miRNAs, miR-27b-3p and miR-193a-5p, were found to inhibit inflammation in AP models.
Area of Science:
- Genetics
- Molecular Biology
- Gastroenterology
Background:
- MicroRNA (miRNA) expression profiles are altered in acute pancreatitis (AP).
- The exact mechanisms underlying these miRNA alterations in AP require further investigation.
Purpose of the Study:
- To identify novel microRNAs (miRNAs) associated with acute pancreatitis (AP) susceptibility.
- To investigate the potential diagnostic utility of identified miRNAs for AP.
- To explore the role of specific miRNAs in regulating inflammatory responses in AP.
Main Methods:
- Mendelian randomization (MR) analysis was used to assess the causal association between miRNA expression and AP susceptibility.
- Genome-wide association study data from the FinnGen Consortium and miRNA expression data were utilized.
- In vitro experiments involving overexpression of miR-27b-3p and miR-193a-5p in cell lines were performed to assess their impact on inflammation.
Main Results:
- Sixty-six miRNAs showed suggestive causality with AP susceptibility, and six miRNAs demonstrated potential for AP diagnosis via ROC curve analysis.
- Changes in acinar cell and monocyte percentages were observed during AP progression and regression in mouse models.
- Overexpression of miR-27b-3p and miR-193a-5p significantly inhibited p-P65 protein expression, indicating reduced inflammation in cell models.
Conclusions:
- Novel miRNAs associated with the pathogenesis of acute pancreatitis (AP) have been identified.
- miR-27b-3p and miR-193a-5p demonstrate potential to inhibit inflammatory responses relevant to AP.
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