Multi-Omics Integration Analysis Revealed That miR-375-3p Is a Two-Sided Factor Regulating the Development and TUMORIGENESIS of Alzheimer’s Disease

TL;DR

This study shows that miR-375-3p has dual roles in Alzheimer's disease and lung cancer, affecting metabolism, cell death, and tumor growth.

Contribution

The study reveals miR-375-3p as a two-sided regulator in Alzheimer’s disease and small cell lung cancer through multi-omics analysis.

Findings

miR-375-3p is differentially expressed in Alzheimer’s disease and small cell lung cancer.

Key genes like ASCL1 and CHD7 are linked to miR-375-3p’s regulatory pathways.

miR-375-3p influences lipid metabolism, apoptosis, and tumor progression in both diseases.

Abstract

It has been reported that miR-375-3p plays a critical role in numerous diseases. To elucidate its biological function, particularly its differential expression and specific mechanisms of action in Alzheimer’s disease (AD) and small cell lung cancer (SCLC), this study comprehensively explores the associations between the target genes of miR-375-3p and both AD and SCLC. The focus is specifically on its impact on disease progression and the remodeling of the tumor microenvironment. We utilized databases such as the miRNA TargetScanHuman 8.0 database and the STRING database, to construct a protein–protein interaction (PPI) network for the classification and discrimination of the miR-375-3p gene, resulting in the identification of 14 intersecting target genes. Subsequently, two key genes, ASCL1 and CHD7, along with their associated genes, were further analyzed using Spearman correlation analysis. The identified key genes were then subjected to GO function annotation and KEGG pathway enrichment analysis. It was determined that pathways related to lipid metabolism, autophagy, and cell apoptosis were differentially expressed in the AD and SCLC environments, with nine related pathways identified, among which the PI3K pathway was the most prominent. Finally, we demonstrated that the expression of miR-375-3p significantly differed between the two environments, with higher expression levels observed in AD compared to SCLC. Our study confirmed that miR-375-3p can promote apoptosis, regulate lipid metabolism, influence the progression of neurodegenerative diseases, and inhibit the proliferation and metastasis of tumor cells. These research findings may have significant implications for the future treatment of AD and SCLC.

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