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Identification of epigenetic interactions between microRNA and DNA methylation associated with polycystic ovarian

Zhanrui Mao1, Ting Li2, Hui Zhao1

  • 1School of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai, 200240, China.

Journal of Human Genetics
|August 8, 2020
PubMed

Insights

Aberrations in microRNA and DNA methylation contribute to polycystic ovarian syndrome (PCOS). This study reveals epigenetic interactions, identifying specific microRNAs and genes involved in PCOS, offering potential therapeutic targets.

Area of Science:

  • Reproductive Endocrinology
  • Epigenetics
  • Genomics

Background:

  • Aberrant microRNA (miRNA) expression and DNA methylation are implicated in the pathogenesis of polycystic ovarian syndrome (PCOS).
  • The intricate epigenetic interplay between miRNA and DNA methylation in PCOS remains largely uncharacterized.

Purpose of the Study:

  • To investigate the epigenetic interactions between miRNA and DNA methylation in the context of PCOS.
  • To identify novel molecular targets for PCOS through integrated omics analysis.

Main Methods:

  • Integrated analysis of RNA-sequencing (RNA-seq), miRNA-sequencing (miRNA-seq), and methylated DNA-binding domain sequencing (MBD-seq).
  • Analysis performed on ovarian granulosa cells from PCOS patients and controls.

Main Results:

  • Identified 830 differentially expressed genes and 30 differentially expressed miRNAs in PCOS.
  • Found 130 miRNA promoters with significant differential methylation, with 13 associated with miRNA expression levels.
  • Demonstrated hypermethylation of miR-429, miR-141-3p, and miR-126-3p promoters, leading to suppressed miRNA expression and subsequent upregulation of target genes (e.g., XIAP, BRD3).

Conclusions:

  • This study provides novel insights into the epigenetic mechanisms underlying PCOS pathogenesis.
  • The observed gene silencing reversal due to epigenetic alterations may play a role in PCOS development.
  • Specific miRNAs and their regulated genes represent potential molecular targets for PCOS therapeutics.

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