Investigation of competing endogenous RNA regulation of BCAS۴ and SHISA۷ in tau pathology in Alzheimer’s disease

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder (NDD) that is increasing inprevalence globally. Emerging data suggest that GABAergic signaling may experience pathogenic changesand contribute to the pathological hallmarks of AD, such as tau phosphorylation. Moreover, it is widelyestablished that a disruption in the equilibrium of competing endogenous RNA (ceRNA) crosstalk plays arole in NDDs [۳; ۴]. In this study, we employed bioinformatic approaches to investigate the ceRNAregulation of BCAS۴ and SHISA۷ in tau pathology. Two microarray datasets were downloaded from theGene Expression Omnibus database, including information on mRNAs (GSE۱۰۶۲۴۱) and miRNAs(GSE۱۵۷۲۳۹) from individuals with AD who had varying degrees of AD-associated neurofibrillarypathology in temporal cortex (TC) tissue specimens and matched controls. The R package limma was usedto discover differentially expressed mRNAs and miRNAs associated with AD-related neurofibrillarypathology. We utilized miRWalk (version ۳) to identify interactions between miRNAs linked with ADrelatedneurofibrillary pathology and BCAS۴/SHISA۷. The ceRNA regulatory axes were constructedutilizing co-expression and miRNA-mRNA interactions. Only Braak stage V exhibited dysregulation of theBCAS۴ and SHISA۷ genes. Hsa-miR-۱۸۵-۵p targeted both genes BCAS۴ and SHISA۷ and its levels ofexpression were statistically higher in TC samples of AD than in controls. Based on co-expression andmiRNA-mRNA interactions, BCAS۴ was proven to act as a ceRNA for SHISA۷ by sponging hsa-miR-۱۸۵-۵p in TC tissue specimens. The current work is the first evidence to highlight the expression of theBCAS۴/hsa-miR-۱۸۵-۵p/SHISA۷ ceRNA axis in the brains of AD patients.

کلیدواژه ها:

Alzheimer’s disease ، BCAS۴ ، competing endogenous RNA ، miR-۱۸۵ ، SHISA۷