Analysis of BCAS4/hsa-miR-185-5p/SHISA7 competing endogenous RNA axis in late-onset Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. Emerging evidence points to the possibility that the GABAergic signaling pathway undergoes pathological alterations and contributes to pathological hallmarks of AD. SHISA7 (CKAMP59) is a new member of the SHISA family. It exhibits a direct function in inhibitory synaptic GABAAR regulation. We used bioinformatics and experimental methods in this research to explore competing endogenous RNA (ceRNA) regulation of BCAS4 and SHISA7 in tau pathogenesis and their capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. Methods: The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD with different degrees of AD-associated neurofibrillary pathology and corresponding controls were downloaded. The limma package in the R software was used to identify differently expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). The ceRNA regulatory axes were built using the co-expression and miRNA-mRNA interactions. Additionally, we used the quantitative polymerase chain reaction technique to examine the expression of the BCAS4/hsa-miR-185-5p/SHISA7 ceRNA axis in the peripheral blood (PB) of fifty AD patients and fifty control subjects. Results: BCAS4 was shown to act as a ceRNA to control the SHISA7 expression throughout AD-associated neurofibrillary pathology in temporal cortex (TC) tissue specimens by sponging hsa-miR-185-5p, based on our bioinformatics study. Furthermore, in PB specimens from individuals suffering from AD and normal controls, we found no substantial differences in BCAS4 expression patterns. SHISA7 expression in AD patients’ PB was found to be reduced, as was the case in the TC. Furthermore, we discovered reduced amounts of hsa-miR-185-5p in AD patients’ PB samples compared to control subjects, unlike in TC tissue, where it had been demonstrated to be overexpressed. Finally, SHISA7 and has-miR-185-5p were shown to be effective in identifying AD patients from healthy controls, according to the receiver operating characteristic (ROC) curve evaluation.