The landscape of miRNA-mRNA regulatory network and cellular sources in inflammatory bowel diseases: insights from text mining and single cell RNA sequencing analysis.

BACKGROUND

Inflammatory Bowel Diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn's Disease (CD), are chronic, recurrent inflammatory conditions of the gastrointestinal tract. The microRNA (miRNA) -mRNA regulatory network is pivotal in the initiation and progression of IBDs. Although individual studies provide valuable insights into miRNA mechanisms in IBDs, they often have limited scope due to constraints in population diversity, sample size, sequencing platform variability, batch effects, and potential researcher bias. Our study aimed to construct comprehensive miRNA-mRNA regulatory networks and determine the cellular sources and functions of key miRNAs in IBD pathogenesis.

METHODS

To minimize potential bias from individual studies, we utilized a text mining-based approach on published scientific literature from PubMed and PMC databases to identify miRNAs and mRNAs associated with IBDs and their subtypes. We constructed miRNA-mRNA regulatory networks by integrating both predicted and experimentally validated results from DIANA, Targetscan, PicTar, Miranda, miRDB, and miRTarBase (all of which are databases for miRNA target annotation). The functions of miRNAs were determined through gene enrichment analysis of their target mRNAs. Additionally, we used two large-scale single-cell RNA sequencing datasets to identify the cellular sources of miRNAs and the association of their expression levels with clinical status, molecular and functional alternation in CD and UC.

RESULTS

Our analysis systematically summarized IBD-related genes using text-mining methodologies. We constructed three comprehensive miRNA-mRNA regulatory networks specific to IBD, CD, and UC. Through cross-analysis with two large-scale scRNA-seq datasets, we determined the cellular sources of the identified miRNAs. Despite originating from different cell types, hsa-miR-142, hsa-miR-145, and hsa-miR-146a were common to both CD and UC. Notably, hsa-miR-145 was identified as myofibroblast-specific in both CD and UC. Furthermore, we found that higher tissue repair and enhanced glucose and lipid metabolism were associated with hsa-miR-145 in myofibroblasts in both CD and UC contexts.

CONCLUSION

This comprehensive approach revealed common and distinct miRNA-mRNA regulatory networks in CD and UC, identified cell-specific miRNA expressions (notably hsa-miR-145 in myofibroblasts), and linked miRNA expression to functional alterations in IBD. These findings not only enhance our understanding of IBD pathogenesis but also offer promising diagnostic biomarkers and therapeutic targets for clinical practice in managing IBDs.