Identification of the function and mechanism of m6A reader IGF2BP2 in Alzheimer’s disease

Abstract

Alzheimer’s disease, the most common form of dementia in the elderly, is a kind of neurodegenerative disease. However, its pathogenesis and diagnosis remain unclear. M6A is related to nervous system development and neurodegenerative diseases. Here in this study, using multiple RNA-seq datasets of Alzheimer’s brain tissues, along with bioinformatic analysis, we innovatively found that m6A reader protein IGF2BP2 was abnormally highly expressed in Alzheimer’s patients. After compared between Alzheimer’s and normal brain samples, and between IGF2BP2- high and IGF2BP2- low subgroups of Alzheimer’s patients, we took the shared differentially expressed genes as the relevant gene sets of IGF2PB2 affecting Alzheimer’s disease occurrence for subsequent analysis. Then, weight gene correlation analysis was conducted and 17 functional modules were identified. The module that most positively correlated with Alzheimer’s disease and IGF2PB2-high subgroups were mainly participated in ECM receptor interaction, focal adhesion, cytokine-cytokine receptor interaction, and TGF-beta signaling pathway. Afterwards, a hub gene-based model including 20 genes was constructed by LASSO regression and validated by ROC curve for Alzheimer diagnosis. Finally, we preliminarily elucidated that IGF2BP2 could bind with mRNAs in a m6A-dependent manner. This study first elucidates the pathogenic role of IGF2BP2 in Alzheimer’s disease. IGF2BP2 and its relevant m6A modifications are potential to be new diagnostic and therapeutic targets for Alzheimer’s patients.

IGF2BP2 maybe a novel prognostic biomarker in oral squamous cell carcinoma

“…The study of Wang et al showed that IGF2BP2 up-regulated the expression of circ 0000745 through microRNA-3187-3p/ErbB4/PI3K/Akt axis and promoted the aggressiveness and stemness of ovarian cancer cells [ 37 ]. Deng et al confirmed that IGF2PB2 can specifically bind to TP53I11, PKP2, BMP6, CFH and COL1A1 , through ECM–receptor interaction, cytokine–cytokine receptor interaction, and TGF-β signaling pathway in Alz play an important regulatory role in Haimer’s disease [ 38 ]. Other research indicates that IGF2BP2 plays a regulatory role in the pathological mechanisms of Lung ischemia–reperfusion injury (LIRI), Hemoglobin H-Constant Spring disease (HbH-CS), Autoimmune inflammation, and other diseases [ 39–41 ].…”

The Role of m6A on Female Reproduction and Fertility: From Gonad Development to Ovarian Aging

“…m 6 A modification have been reported to be involved in regulating the proliferation, differentiation, and apoptosis of bone-related cells including bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts by multiple studies ( Huang et al, 2021 ) ( Wang et al, 2021b ; Chen et al, 2022 ) ( Wu et al, 2020 ). In addition, IGF2BP2 highly expressed in Alzheimer’s patients by bioinformatic analysis using multiple RNA-seq datasets of Alzheimer’s brain tissues ( Deng et al, 2021 ). Su et al found that age difference impacted m 6 A RNA methylation in hearts and their response to acute myocardial ischemia/reperfusion (I/R) injury ( Su et al, 2021 ).…”

“…To date, increasing research have reported the connection between m 6 A and organ aging/cell senescence. However, most of them mainly focused on methyltransferase, such as METTL3/METTL14 ( Zhang J. et al, 2020 ; Wu et al, 2020 ; Liu et al, 2021 ; Chen et al, 2022 ), and the demethylases and readers were gradually concerned in recent years, including ALKBH5 ( Li et al, 2022a ), WTAP ( Li et al, 2022b ), IGF2BP2 ( Deng et al, 2021 ). Notedly, in reproductive aging, FTO has been shown to play the regulatory role ( Ding et al, 2018 ; Zhou L. et al, 2021 ; Jiang et al, 2021 ; Sun et al, 2021 ).…”

Metabolomics Study Suggests the Mechanism of Different Types of Tieguanyin (Oolong) Tea in Alleviating Alzheimer’s Disease in APP/PS1 Transgenic Mice

“…Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive loss, which is mainly manifested as progressive memory dysfunction, cognitive dysfunction, personality abnormalities and language impairment [ 1 ]. AD is a disease that typically increases in incidence with age, with an incidence of less than 1% in the 60–64 age group, and the incidence increases exponentially with age.…”