NSUN2 ‐mediated m 5 C methylation modification regulates trophoblast cell proliferation, apoptosis, and autophagy in gestational diabetes mellitus
Year: 2025
Type: article
Abstract: ABSTRACT Introduction Gestational diabetes mellitus (GDM) represents one of the most prevalent medical complications during pregnancy. Emerging evidence has implicated NOL1/NOP2/SUN domain (NSUN)2‐mediated 5‐methylcytosine (m 5 C) methylation modifications in various pathological conditions. This study aimed to investigate the role of m 5 C modification in GDM and to elucidate its underlying mechanisms. Materials and Methods The mRNA expression levels of m 5 C‐related RNA methyltransferases were quantified using reverse transcription‐quantitative polymerase chain reaction. Cellular viability and proliferation were assessed through Cell Counting Kit‐8 and EdU assays. The apoptosis rate was determined by flow cytometry. Western blot was employed to analyze autophagy‐related protein expression. The m 5 C modification sites on PTEN‐induced putative kinase 1 (PINK1) were identified via dual‐luciferase reporter assays. An RNA immunoprecipitation assay was performed to examine NSUN2‐PINK1 interactions. Finally, a mouse model was established to further explore the role of NSUN2 in GDM in vivo . Results Our findings revealed elevated NSUN2 expression in HTR‐8/SVneo cells. NSUN2‐mediated m 5 C modification suppressed proliferation while enhancing apoptosis, inflammation, and autophagy in high glucose (HG)‐stimulated HTR‐8/SVneo cells. Mechanistically, NSUN2 upregulated PINK1 expression through an m 5 C‐dependent regulation. Pharmacological inhibition of PINK1 reversed these effects, enhancing proliferation while attenuating apoptosis, inflammation, and autophagy under HG conditions. Conversely, PINK1 overexpression exacerbated the observed cellular responses. In vivo , NSUN2 inhibition alleviated inflammation and hyperglycemia in GDM pregnant mice. Conclusions NSUN2‐mediated m 5 C modification promoted GDM progression by upregulating PINK1 expression, leading to impaired trophoblast function. Targeting this NSUN2‐m 5 C‐PINK1 axis may represent a promising therapeutic strategy for GDM management.
DOI: 10.1111/jdi.70140
Authors: Jiujiu Liu, Yingjun Chen, Dapeng Wang, Zhaozhao Li
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,850
OpenAlex ID: W4413797573