miR-451a Inhibition Reduces Established Endometriosis Lesions in Mice

Reprod Sci. 2019 Nov;26(11):1506-1511. doi: 10.1177/1933719119862050. Epub 2019 Jul 28.

Abstract

Endometriosis is an estrogen-dependent pro-inflammatory disease that affects 6% to 10% of reproductive-age women. Current treatments target sex steroids, and none are disease-specific. MicroRNA treatments have provided promising results for some chronic diseases and cancers. We have previously shown microRNA 451a is increased in endometriosis and that elevation of 451a contributes to the pathophysiology of the disease. Here, we propose inhibition of miR-451a for the treatment of endometriosis in a murine model. Endometriosis was treated using a microRNA 451a inhibitor or a scrambled control microRNA. Treatment with miR-451a inhibitor resulted in reduced endometriosis lesion size (30 vs 13 mm3). There was no difference in the number of visible lesions between the miR-451a treatment and controls. Treatment led to altered expression of several genes including YWHAZ, CAB39, MAPK1, β-catenin, and IL-6. Systemic treatment with a miR-451a inhibitor is a promising therapy for endometriosis that simultaneously affects multiple pathways driving the disease.

Keywords: endometriosis; miR-451; microRNA; oligonucleotide treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endometriosis / drug therapy*
  • Endometriosis / genetics
  • Endometriosis / metabolism*
  • Female
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • MicroRNAs / pharmacology
  • MicroRNAs / therapeutic use

Substances

  • MicroRNAs
  • Mirn451 microRNA, mouse