Levonorgestrel Ameliorates Adenomyosis via lncRNA H19/miR-17/TLR4 Pathway

Drug Des Devel Ther. 2020 Aug 24:14:3449-3460. doi: 10.2147/DDDT.S248095. eCollection 2020.

Abstract

Purpose: To explore the mechanism of levonorgestrel (LNG)-ameliorating adenomyosis through long non-coding RNA H19 (lncRNA H19)/miR-17/Toll-like receptor 4 (TLR4) pathway.

Patients and methods: A total of 71 cases of adenomyosis and 54 cases of normal endometrium were sampled. Quantitative polymerase chain reaction (qPCR) was employed to quantify lncRNA H19, miR-17, and TLR4 mRNA, while Western blot (WB) was used to quantify TLR4 protein. Effects of LNG on normal endometrial stromal cells (ESCs) were evaluated. Suppression/over-expression vectors of lncRNA H19, miR-17, and TLR4 were constructed to observe their effects on ESCs.

Results: MiR-17 and TLR4 mRNA were up-regulated and lncRNA H19 was down-regulated in adenomyosis. After LNG treatment, lncRNA H19 was up-regulated while miR-17 and TLR4 were down-regulated. LNG, up-regulation of lncRNA H19, and down-regulation of miR-17 and TLR4 portend increased apoptosis, G1-arrested cells, as well as inhibited inflammation. Dual-luciferase reporter (DLR) assay conformed the targeting relation of lncRNA H19/miR-17/TLR4 pathway.

Conclusion: LNG ameliorates adenomyosis via lncRNA H19/miR-17/TLR4 pathway.

Keywords: adenomyosis; levonorgestrel; lncRNA H19/miR-17/TLR4 pathway.

MeSH terms

  • Adenomyosis / drug therapy*
  • Adenomyosis / metabolism
  • Adenomyosis / pathology
  • Adult
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • Levonorgestrel / pharmacology*
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • H19 long non-coding RNA
  • MIRN17 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Levonorgestrel