microRNA Let-7b: A Novel treatment for endometriosis

J Cell Mol Med. 2018 Nov;22(11):5346-5353. doi: 10.1111/jcmm.13807. Epub 2018 Jul 31.

Abstract

Endometriosis is an oestrogen-dependent, chronic inflammatory disease that affects 10% of reproductive-aged women. Current treatment options depend on female sex steroid hormone modulation; however, all have side effects and are not useful in women who want to conceive. microRNAs treatments have provided promising results for some chronic diseases and cancers. We have previously shown the microRNA Let-7b is repressed in endometriosis and that loss of Let-7 contributes to the pathophysiology of the disease. Here, we propose using microRNA Let-7b for the treatment of endometriosis in a murine model. Endometriosis was treated using microRNA Let-7b or a scrambled control microRNA. Let-7b treatment resulted in reduced endometriosis lesion size. Decreased gene expression was noted in several genes known to promote endometriosis growth including ER-α, ER-ß, Cyp19a, KRAS 4A, KRAS 4B and IL-6. These results indicate that microRNA Let-7b has a pleiotropic role in endometriosis pathophysiology affecting oestrogen signalling, inflammation and growth factor receptors. Local treatment of endometriosis with Let-7b is a promising therapy for endometriosis that simultaneously affects multiple pathways driving endometriosis without systemic hormonal side effects.

Keywords: endometriosis; miRNA Let-7b; microRNA; oligonucleotide treatment.

Publication types

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

MeSH terms

  • Animals
  • Aromatase / genetics
  • Disease Models, Animal
  • Endometriosis / genetics
  • Endometriosis / pathology
  • Endometriosis / therapy*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor beta / genetics
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Inflammation / therapy*
  • Interleukin-6 / genetics
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / therapeutic use
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Signal Transduction / genetics

Substances

  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Interleukin-6
  • KRAS protein, human
  • MicroRNAs
  • mirnlet7 microRNA, human
  • Aromatase
  • CYP19A1 protein, human
  • Proto-Oncogene Proteins p21(ras)