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Published on: March 30, 2019

Hypoxia-induced microRNA-20a expression increases ERK phosphorylation and angiogenic gene expression in endometriotic

Shih-Chieh Lin1, Chih-Chuan Wang, Meng-Hsing Wu

  • 1Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.

The Journal of Clinical Endocrinology and Metabolism
|June 1, 2012
PubMed
Abstract

Insights

MicroRNA-20a (miR20a) is upregulated in endometriosis, promoting cell proliferation and angiogenesis by activating MAPK signaling. This study reveals miR20a as a key player in endometriosis development.

Area of Science:

  • Molecular Biology
  • Reproductive Medicine
  • Genetics

Background:

  • Aberrant mitogen-activated protein kinase (MAPK) pathway activation is implicated in endometriosis pathogenesis.
  • The precise mechanisms of MAPK activation in endometriotic tissues are not fully understood.
  • MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and are implicated as modulators of transcriptional responses.

Purpose of the Study:

  • To investigate the functional role of microRNA-20a (miR20a) in MAPK pathway activation.
  • To elucidate the involvement of miR20a in the pathogenesis of endometriosis.

Main Methods:

  • Quantitative RT-PCR was used to analyze miR20a expression in endometrial and endometriotic tissues.
  • Overexpression and inhibition of miR20a in endometrial and endometriotic stromal cells, respectively.
  • Assessment of extracellular signal-regulated kinase (ERK) phosphorylation and expression of angiogenesis- and proliferation-related genes.

Main Results:

  • miR20a levels were significantly elevated in endometriotic stromal cells, induced by hypoxia-inducible factor-1α.
  • Upregulated miR20a led to decreased dual-specificity phosphatase-2, prolonged ERK phosphorylation, and increased expression of angiogenic genes.
  • miR20a enhanced prostaglandin E(2)-induced fibroblast growth factor-9 expression, promoting cell proliferation.

Conclusions:

  • A novel mechanism linking hypoxic stress, miR20a upregulation, aberrant ERK phosphorylation, and angiogenesis in endometriosis was identified.
  • miR20a is demonstrated to be a critical modulator in the development of endometriosis.

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