A computational approach to identify the biomarker based on the RNA sequencing data analysis for Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease. AD affects at least ۲۷ million people and is associated with a high impact on the life of the patient’s family and a huge financial cost to society. RNA sequencing (RNA-seq) is one effective approach to finding the heterogeneous gene expressions of diseases that helps discover new functional genes as prognostic biomarkers. Besides, It is well-known that microRNA (miRNAs) biomarkers have emerged as a powerful screening tool, as they are highly expressed in AD patients and easily detectable in several biological samples. The bioinformatics method is cost-effective and time-saving when studying the role of miRNAs-mRNA. Therefore, in this study computational models were used to identify AD-related biomarkers by RNA-seq analysis. The RNA sequencing of ۴۰ AD samples with ۸ healthy control tissue from the occipital lobe under the accession code GSE۲۰۳۲۰۶ were obtained from the GEO database. The differentially expressed genes (DEGs) between AD and normal tissues were obtained by using GEO۲R. The ۱۰۰۰ top upregulated genes were imported into the STRING (version ۱۲.۰, http://string-db.org) database to identify the interactive association between the proteins. Then, all interactions with a significant combined score >۰.۴ were selected for further analysis. The appropriate gene with the highest degrees of connectivity were selected as hub genes. The targetScan database is a specialized collection of microRNA-mRNA targeting relationships. These databases were used to obtain hub gene-associated miRNA. This study identified ۴۱۵۰ genes with |log۲FC|>۰.۵ and P-value <۰.۰۱ as DEGs: ۱۲۷۹ upregulated and ۲۸۷۱ downregulated genes. γ-aminobutyric acid receptors β۲ subunit gene (GABRB۲) was identified as one of the best hub genes in STRING which hsa-miR-۹-۵p can suppress the GABRB۲ expression in AD. GABRB۲ has a pivotal role in the central nervous system. Several studies also reported alterations in GABA levels, typically a reduction in total neurotransmitter concentration in several regions of the post-mortem AD brain. As recorded, miR-۹-۵p is found to be downregulated in the brain of the AD patients. Overexpression of miR-۹-۵p modulates neuroinflammation in the central nervous system. Of note, these bioinformatic results confirmed that targeting GABRB۲ is an important mechanism of AD function improving by miR-۹-۵p in AD. Moreover, TargetScan indicates that the seed region of miR-۹-۵p contains ۲ complementary sites within position ۴۶۴۵-۴۶۵۲ and ۴۷۲۶-۴۷۳۲ of GABRB۲ ۳' UTR. Taken together, our findings from RNA sequencing analysis provide the first clues regarding the role of miR-۹-۵p as a modulator of the progression of AD by inhibiting GABRB۲ translation. The results also provide valuable insights into the regulation of miR-۹-۵p and GABRB۲ for future research and therapeutic development. These can be used as a specific diagnostic index and therapeutic target for patients with AD.

کلیدواژه ها:

Alzheimer’s disease ، RNA sequencing ، miRNA ، miR-۹-۵p ، GABRB۲