Exploring the role of miR-125b-5p as a pro-inflammatory factor in Alzheimer's disease pathology

Alzheimer's disease (AD) is a common neurodegenerative disease, where neuroinflammation significantly influences its pathophysiology by driving the disease's pathological cascade. As a pro-inflammatory regulator, miR-125b-5p contributes to AD progression, though its precise role and mechanisms remain unclear.

We aims to identify mRNAs significantly regulated by pro-inflammatory miR-125b-5p in AD and uncover key neuroinflammatory pathways.

Target mRNAs regulated by miR-125b-5p were predicted using online databases and analyzed with two mRNA datasets to identify differentially expressed mRNAs (DEmRNAs). Enrichment analysis was conducted to explore their biological functions and pathways. The significance of DEmRNAs expression in AD-related inflammatory pathways was verified by the Wilcoxon test, predictive accuracy was assessed via area under the curves (AUCs), and novel mRNAs were identified through positive control analysis.

A total of 613 miR-125b-5p target mRNAs were identified, and 44 DEmRNAs were detected to be regulated by miR-125b-5p in two datasets. The 44 target DEmRNAs associated with AD include three key pathways: insulin signaling (EXOC7, FLOT2, MKNK2), phosphatidylinositol signaling (IP6K1, MTMR3), and phospholipase D signaling (CYTH1, GAB2). Correlation analysis indicated strong correlations among 7 mRNAs, all showing significant differential expression, with AUCs above 0.5, confirming their predictive value. Three mRNAs (EXOC7, IP6K1, CYTH1) were identified as novel AD-related genes. MiR-125b-5p binding sites in the 3'-UTRs of these 7 mRNAs suggest their potential roles in AD-related inflammation and signaling pathways.

This study investigates the pro-inflammatory miR-125b-5p's role in the pathological processes of AD, highlighting its regulation of key target mRNAs and critical pathways.