Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

A comprehensive molecular study of hsa-miR-140-5p and hsa-miR-31-5p and their target genes MMP9, TNF-α, TGFB1, and SCN2A in patients with comorbid Alzheimer’s disease and epilepsy

Articles in Press

Document Type : Original Article

Authors
Saghar Zonnar 1
Jafar Amani 2
Iman Salahshouri Far 1
1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
10.22038/ijbms.2026.94894.20499
Abstract
Objective(s): Alzheimer’s disease (AD) and epilepsy show significant bidirectional clinical comorbidity, yet their shared peripheral molecular mechanisms remain poorly characterized. This study investigated potential dysregulation of hsa-miR-140-5p and hsa-miR-31-5p, along with their target genes (MMP9, TNF-α, TGFB1, SCN2A), in patients with comorbid AD and epilepsy.
Materials and Methods: A multi-tiered study was conducted, combining a systematic bioinformatic meta-analysis of five public GEO datasets (over 500 samples) with experimental validation using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and MALDI-TOF mass spectrometry in plasma from 20 comorbid patients and 20 age- and sex-matched healthy controls.
Results: Bioinformatic screening identified a prominent inflammatory network. Experimental validation revealed significant up-regulation of MMP9 (3.92-fold, P<0.0001) and TNF-α (2.21-fold, P=0.023) in comorbid patients. Conversely, hsa-miR-140-5p, a predicted repressor of MMP9, was significantly down-regulated (0.45-fold, P=0.008), demonstrating a strong inverse correlation with MMP9. Paradoxically, hsa-miR-31-5p was significantly up-regulated (2.8-fold, P<0.001). Changes in TGFB1 and SCN2A expression were not statistically significant. Proteomic profiling via MALDI-TOF identified 57 differentially abundant peptide peaks, confirming exclusive detection of Aβ1-42, the loss of neurogranin-derived peptides (absent in patients), and elevated MMP9 proteolytic fragments in the patient group.
Conclusion: These preliminary findings indicate a shared peripheral molecular signature involving hsa-miR-140-5p, hsa-miR-31-5p, MMP9, and TNF-α. This highlights neuroinflammatory pathways as shared features of comorbid AD and epilepsy, warranting further evaluation in larger longitudinal cohorts.
Keywords
Alzheimer disease
Comorbidity
Epilepsy
Matrix metalloproteinase
MicroRNAs
Neuroinflammation
Tumor necrosis factor-alpha
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 07 October 2026