The Relationship between the Aberrant Long Non-Coding RNA-Mediated Competitive Endogenous RNA Network and Alzheimer’s Disease Pathogenesis

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by cognitive dysfunction. The role of long non-coding RNAs (lncRNAs) with the action of competitive endogenous RNA (ceRNA) in AD remains unclear. The present study aimed to identify significantly differentially expressed lncRNAs (SDELs) and establish lncRNA-associated ceRNA networks via RNA sequencing analysis and a quantitative real-time Polymerase Chain Reaction (qPCR) assay using transgenic mice with five familial AD mutations. A total of 53 SDELs in the cortex and 51 SDELs in the hippocampus were identified, including seven core SDELs common to both regions. The functions and pathways were then investigated through the potential target genes of SDELs via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, which indicate biological effects, action distributions, and pathological transductions associated with AD. Based on the ceRNA hypothesis, integrated ceRNA networks in the cortex and hippocampus of lncRNA-miRNA-mRNA were constructed. The core SDEL-mediated ceRNA relationship was established and the expression of these RNAs was verified by qPCR. The results identified lncRNA ENSMUST00000127786 and highlighted miRNAs and mRNAs as potential key mediators in AD. These findings provide AD-derived lncRNA-mediated ceRNA profiles, and further experimental evidence is needed to confirm these identified ceRNA regulatory relationships.

Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model

“…The Morris water maze (MWM) test was used to evaluate the impairment of spatial learning and memory of 5 × FAD mice ( Liu et al, 2018 ; Jiang et al, 2022 ; Sun et al, 2022 ). A different cohort from the Cai et al (2022) study was used for MWM test. Briefly, The testing included place navigation training and space memory trials.…”

“…The total RNA of the hippocampus was isolated with TRIzol reagent (Invitrogen, CA, United States) according to the previous protocol ( Zhao et al, 2022 ). The RNA sample used in this study was the same cohort as our reported investigation ( Cai et al, 2022 ). Subsequently, the RNA integrity was determined using gel electrophoresis ( Supplementary Figure 1 ).…”

The role of noncoding RNA and its diagnostic potential in intrahepatic cholestasis of pregnancy: a research update

“…The ceRNA hypothesis proposes that RNA transcripts, both coding and noncoding, crosstalk with and regulate each other via microRNA response elements (Thomson and Dinger, 2016). The ceRNA hypothesis suggests that the regulatory interactions between different RNA types are important for the development, progression, and regulation of various diseases, including cancer, cardiovascular diseases, and neurological disorders (Cai et al, 2022;Liang et al, 2020;. Furthermore, increasing evidence suggests that ceRNAs play a vital role in reproductive health, including fetal development, preeclampsia, gestational diabetes, and spontaneous abortion (Gan et al, 2022;Jain et al, 2022;Leng et al, 2019;S.…”

Role of traditional Chinese medicine in ameliorating mitochondrial dysfunction via non-coding RNA signaling: Implication in the treatment of neurodegenerative diseases

“…Excessive mitochondrial fission promotes mitophagy through the PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy pathway, with a convergence of the miR-351-5p/MIRO2 axis in the pathology of AD (Chen et al, 2016). With the ongoing development of high-throughput sequencing and microarray technologies, many novel ncRNAs with regulatory roles in NDs are being identified (Cai et al, 2022b;Sun et al, 2022b;Zhao et al, 2022). For example, miR-455-3p is a newly discovered miRNA that showed significant upregulation in AD (Kumar et al, 2017), and its overexpression positively regulated the expression of mitochondrial biogenesis genes.…”