Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer's disease

Qi Zhang; Bishuang Chen; Ping Yang; Jipan Wu; Xinping Pang; Chaoyang Pang

doi:10.3389/fgene.2022.1049786

Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer's disease

Front Genet. 2022 Nov 18:13:1049786. doi: 10.3389/fgene.2022.1049786. eCollection 2022.

Authors

Qi Zhang¹, Bishuang Chen¹, Ping Yang¹, Jipan Wu¹, Xinping Pang², Chaoyang Pang¹

Affiliations

¹ School of Computer Science, Sichuan Normal University, Chengdu, China.
² West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.

Abstract

Alzheimer's disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by β-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites (miRNA response elements, MREs), which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) and microRNAs (miRNAs) in Alzheimer's disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer's disease patients (GSE5281, GSE122603, GSE97760, GSE150693, GSE1297, and GSE161435). Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by MAPT and AP2M1, were identified by the mediation center algorithm, 34 miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs and mRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer's disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer's disease. Furthermore, the ncRNAs found here might become novel biomarkers and potential targets for the development of Alzheimer's drugs.

Keywords: Alzheimer’s disease; GEO; biomarkers; ceRNA; circRNA; miRNA; prognosis.