Systems-level bioinformatics analysis of hsa-miR-132-3p targets identifies a conserved neuroimmune regulatory module relevant to Alzheimer's disease.

Authors

Ismael Soltani, Wael Bahia, Chaker Slaymi, Wahid Khemissi, Najoua Rahali, Hajer Bougatef, Narjes Baazaoui, Salima Ferchichi, Wassim Y Almawi

Published in

Computational biology and chemistry. Volume 126. Issue Pt 1. Pages 109445. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Alzheimer's disease (AD) arises from converging neurodegeneration and neuroinflammation, yet post-transcriptional mechanisms linking these processes remain poorly defined. Hsa-miR-132-3p, a neuron-enriched microRNA consistently downregulated in AD, has emerged as a candidate integrator of synaptic plasticity and innate immune signaling. Targets of hsa-miR-132-3p were collected from five repositories (miRTarBase v10.0, DIANA-TarBase v9.0, ENCORI v3.0, miRWalk v3.0, miRDB v6.0) and integrated using multiMiR. Functional annotation used ShinyGO v0.81 (KEGG, GO-BP), with immune enrichment via MSigDB Hallmark, ImmPort, and InnateDB. High-confidence targets were defined by overlap with TargetScan conserved predictions and MalaCards AD genes. PPI networks were built with STRING v12.0/MCODE, and transcriptomic validation used GSE5281 hippocampal microarray data. Integration of five repositories identified 5429 non-redundant candidate targets, with significant enrichment in prefrontal cortex and CD33 + myeloid cell signatures (adjusted p < 0.05). Immune analyses highlighted TNFα/NF-κB, IL-6/JAK-STAT3, and interferon signaling overrepresentation. Intersection with TargetScan conserved predictions and MalaCards prioritized a 14-gene module (GSK3B, MAPK1, MAPK3, EP300, FOXO3, PIK3CA, PPP3CA, MAPT, EGR1, NR4A2, SLC30A6, ADCYAP1, SLC6A3, SV2A) defined by the convergence of experimentally supported target annotations, conserved TargetScan predictions, and AD-associated gene annotations. PPI mapping identified MAPK1, MAPK3, EP300, MAPT, and EGR1 as a central interaction module associated with inflammatory signaling and tau-associated processes. Hippocampal transcriptomic analysis provided exploratory evidence of overlap between candidate hsa-miR-132-3p targets and AD-associated differentially expressed genes (KDM4B,CBX3 and MORF4L2). This analysis nominates hsa-miR-132-3p as a candidate post-transcriptional regulator potentially linking neuronal stress, tau pathology, and innate immune signaling in AD. The 14-gene module provides a hypothesis-generating framework for cell-type-resolved experimental validation.

PMID:
42828976
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.

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