miRNA 和 DNA 甲基化之间的调控相互作用协调着多囊卵巢综合征的重要卵巢功能和相关特征。

IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY
Gene Pub Date : 2024-12-14 DOI:10.1016/j.gene.2024.149165
Snehal Bhingardeve, Pooja Sagvekar, Sadhana Desai, Vijay Mangoli, Richa Jagtap, Srabani Mukherjee
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引用次数: 0

摘要

本文章由计算机程序翻译,如有差异,请以英文原文为准。
The regulatory interplay between miRNA and DNA methylation orchestrates vital ovarian functions and associated traits in PCOS.

Polycystic ovary syndrome (PCOS) is the leading cause of amenorrhea and anovulatory infertility in women of reproductive age. Both gene polymorphisms and tissue-specific epigenetic alterations, which determine gene transcription and translation dynamics in disease-states, strongly influence PCOS development. Particularly, promoter-proximal DNA methylation and microRNA expression changes show strong associations with follicular defects, suggesting post-transcriptional dysregulation of localized gene networks. Our recent methylome study and other studies, posit DNA methylation as a regulator of microRNA expression in PCOS. Here, we identified microRNAs, potentially regulated by DNA methylation, and investigated whether their altered expression influences target gene expression in the PCOS ovary. Using granulosa cell samples of women with PCOS and age-BMI matched controls, we evaluated the transcript levels of 14 microRNAs participating in different ovarian processes and assessed their CpG-DNA methylation levels. For 9 of these microRNAs, which revealed differential methylation consistent with their gene hypomethylation or hypermethylation profiles, we evaluated the expression of their predicted, proteincoding target transcripts. Our data indicated that microRNA hypermethylation and decreased transcription of miR-10b-5p, miR-127-3p, miR-5189, miR-410-3p and miR23a-3p were consistent with the upregulation of PTEN, MMP13, OLR1, TET3 and APAF1 in PCOS. Conversely, microRNA hypomethylation and increased expression of miR-140-5p, miR-182-3p, miR-200b-5p and miR-3687 were consistent with downregulation of FZD6, LRP6, ZEB1 and LDLR. However, these observations need robust validations in larger study cohorts complemented with functional and mechanistic studies. Overall, our study indicates that altered microRNA expression as a consequence of DNA methylation changes, may contribute to metabolic and reproductive dysfunction in PCOS.

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来源期刊
Gene
Gene 生物-遗传学
CiteScore
6.10
自引率
2.90%
发文量
718
审稿时长
42 days
期刊介绍: Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.
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