Increased circulating miR-370-3p regulates steroidogenic factor 1 in endometriosis

Am J Physiol Endocrinol Metab. 2019 Mar 1;316(3):E373-E382. doi: 10.1152/ajpendo.00244.2018. Epub 2018 Dec 21.

Abstract

Endometriosis is a gynecologic disease common among reproductive-aged women caused by the growth of endometrial tissue outside the uterus. Altered expression of numerous genes and microRNAs has been reported in endometriosis. Steroidogenic factor 1 (SF-1), an essential transcriptional regulator of multiple genes involved in estrogen biosynthesis, is aberrantly increased and plays an important role in the pathogenesis of endometriosis. Here, we show the expression of SF-1 in endometriosis is regulated by miR-370-3p. Sera and tissue were collected from 20 women surgically diagnosed with endometriosis and 26 women without endometriosis. We found that miR-370-3p levels were decreased in the serum of patients with endometriosis while SF-1 mRNA levels were inversely upregulated in endometriotic lesions compared with respective controls. Transfection of primary endometriotic cells with miR-370-3p mimic or inhibitor resulted in the altered expression of SF-1 and SF-1 downstream target genes steroidogenic acute regulatory protein (StAR) and CYP19A1. Overexpression of miR-370-3p inhibited cell proliferation and induced apoptosis in endometriotic cells. This study reveals that miR-370-3p functions as a negative regulator of SF-1 and cell proliferation in endometriotic cells. We suggest a novel therapeutic strategy for controlling SF-1 in endometriosis.

Keywords: SF-1; apoptosis; cell proliferation; endometriosis; miR-370-3p.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics*
  • Steroidogenic Factor 1 / genetics*
  • Steroidogenic Factor 1 / metabolism
  • Stromal Cells / metabolism
  • Young Adult

Substances

  • MIRN370 microRNA, human
  • MicroRNAs
  • NR5A1 protein, human
  • Steroidogenic Factor 1