Genome-wide DNA methylation changes in oral submucous fibrosis

Kundu, P and Pant, I and Jain, R and Rao, SG and Kondaiah, P (2022) Genome-wide DNA methylation changes in oral submucous fibrosis. In: Oral Diseases, 28 (4). pp. 1094-1103.

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Abstract

Objective: Oral submucous fibrosis (OSF) is a debilitating potentially malignant condition of the buccal cavity characterized by extensive extracellular matrix deposition resulting in stiffness and trismus. As OSF is a progressive disease, we hypothesized that there would be extensive epigenetic changes in OSF tissues. Materials and Methods: Using the Infinium HumanMethylation450 BeadChip Array, we analyzed gross DNA methylation changes in seven OSF tissues compared to five controls. Comparison with transcriptomic data and pathway analyses was conducted to find commonly regulated genes. Results: A total of 3,294 differentially methylated regions mapping to 857 genes were identified. Comparison with transcriptome data revealed 38 downregulated-hypermethylated genes and 55 hypomethylated-upregulated genes. Using methylation-specific and qRT-PCR, aberrant hypomethylation and increased expression of FGF13, RPS6KA3, and ACSL4 genes were confirmed. Pathways involved in insulin signaling, ubiquitin-mediated proteolysis, nicotine addiction, and RAS/MAPK pathways were dysregulated, among others. Intriguingly, numerous genes located on the X chromosome were dysregulated in OSF tissues as the transcript for XIST gene was downregulated due to hypermethylation of the XIST promoter. Conclusions: This study highlights global epigenetic dysregulation of tissues of the oral cavity in OSF patients and hints at possible X chromosomal dysregulation, previously not implicated in the pathogenesis of OSF.

Item Type:	Journal Article
Publication:	Oral Diseases
Publisher:	Blackwell Publishing Ltd
Additional Information:	The copyright for this article belongs to the Blackwell Publishing Ltd.
Keywords:	Areca Nut; Buccal Mucosa; Fibroblast Growth Factor; hypomethylation; TGF-β; X chromosome
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	22 Mar 2021 11:53
Last Modified:	24 Jun 2022 05:04
URI:	https://eprints.iisc.ac.in/id/eprint/68553

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