Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma

Abstract

Chronic asthma is characterized by airway inflammation and irreversible airway remodeling. Epithelial-mesenchymal transition (EMT) is a typical pathological change of airway remodeling. Our previous research demonstrated miR-23b inhibited airway smooth muscle proliferation while the function of miR-23b-3p has not been reported yet. Besides, miRNA is regulated by many factors, including DNA methylation. The function of miR-23b-3p and whether it is regulated by DNA methylation are worth exploring. Balb/c mice were given OVA sensitization to develop the asthmatic model. Expression of miR-23b-3p and EMT markers were measured by RT-qPCR, WB and immunohistochemistry (IHC). DNA methylation was detected by methylation-specific PCR (MSP) and the MassARRAY System. Asthmatic mice and TGF-β1-stimulated bronchial epithelial cells (BEAS-2B) showed EMT with increased miR-23b-3p. Overexpression of miR-23b-3p promoted EMT and migration, while inhibition of miR-23b-3p reversed these transitions. DNA methyltransferases were decreased in asthmatic mice. MSP and MassARRAY System detected the promotor of miR-23b showed DNA hypomethylation. DNA methyltransferase inhibitor 5’-AZA-CdZ increased the expression of miR-23b-3p. Meanwhile, PTEN was identified as a target gene of miR-23b-3p. Our results indicated that promotor hypomethylation mediated upregulation of miR-23b-3p targets PTEN to promote EMT in chronic asthma. miR-23b-3p and DNA methylation might be potential therapeutic targets for irreversible airway remodeling.

A Methylation Diagnostic Model Based on Random Forests and Neural Networks for Asthma Identification

“…This was the first study to utilize DNA methylation-based machine learning to identify a series of asthma-related methylation loci (DECs). Interestingly, the selected methylation signatures were associated with actin cytoskeleton organization and cell-adhesion substrate, shigellosis, and serotonergic synapses, supporting the hypothesis that airway structural reorganization in asthma results from changes in DNA methylation in the epigenetic group [ 28 , 29 ]. Then, ten distinct specific DECs were identified based on RF, and ANN model was built by calculating the weight coefficient of ANN.…”

The potential of targeting microRNA-23b-3p signaling in Alzheimer’s disease: opinions on recent findings

“…Emerging evidence suggests additional targets for miR-23b-3p in non-cancerous diseases, such as neuropilin 1 ( Xia et al, 2020 ), apoptotic protease activating factor-1 (Apaf-1) ( Chen et al, 2014 ), α-synuclein (Geng et al, 2023), and phosphatase and tensin homolog (PTEN) ( Guo et al, 2022 ). Among these, Apaf-1 mediates apoptosis via recruitment and activation of caspase-9 by binding with cytochrome c .…”

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets

“…Previous studies confirmed that miRNAs play an essential role in allergic diseases by influencing Th1/Th2 polarization and Tregs cell/Th17 cell imbalance, promoting epithelial chronic inflammation and tissue remodeling, and activating intrinsic immune cells [ 11 , 27 , 28 ]. Recently, researchers screened and validated various miRNAs that affected the development of AS by regulating immune cell function and promoting the release of inflammatory mediators [ 29 – 31 ]. Mattes et al [ 32 ] reported that airway hyperactivity and inflammation might be reduced by inhibiting miR-126 expression, which could affect CD4 + T cell differentiation towards Th2 and the release of inflammatory cytokines.…”