Linc-ROR Promotes EMT by Targeting miR-204-5p/SMAD4 in Endometriosis

Reprod Sci. 2023 Sep;30(9):2665-2679. doi: 10.1007/s43032-023-01204-0. Epub 2023 Mar 14.

Abstract

Endometriosis (EMs) is a systemic and chronic disease with cancer-like feature, namely, distant implantation, which caused heavy healthy burden of nearly 200 million females. LncRNAs have been proved as new modulators in epithelial-mesenchymal transition (EMT) and EMs. Quantitative real-time PCR was conducted to measure the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (Linc-ROR), and miR-204-5p in ectopic endometrium (n = 25), eutopic endometrium (n = 20), and natural control endometrium (n = 22). Overexpression of Linc-ROR, knockdown or overexpression of miR-204-5p in End1/E6E7 and Ishikawa cells, was conducted to detect the function of Linc-ROR and miR-204-5p in EMs. Furthermore, luciferase reports were used to confirm the combination of Linc-ROR and miR-204-5p and the combination between miR-204-5p and SMAD4. Cell-Counting Kit-8, EdU assay, transwell assays, and Western blotting were used to detect the function of Linc-ROR and miR-204-5p in EMs cancer-like behaviors and EMT process. Linc-ROR was up-regulated in ectopic endometrium. Overexpressed Linc-ROR promotes cell proliferation, invasion, and EMT process. Linc-ROR regulated the EMT process, cellular proliferation, and invasion of EMs via binding to miR-204-5p. In addition, overexpression of Linc-ROR up-regulated SMAD4, a target protein of miR-204-5p, with which regulated EMT process and cancer-like behaviors in EMs together. Linc-ROR/miR-204-5p/SMAD4 axis plays a vital role in regulation EMT process in EMs, which might become a novel therapeutic targets and powerful biomarkers in EMs therapy.

Keywords: EMT; Endometriosis; Linc-ROR; SMAD4; ceRNA; miR-204-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Endometriosis* / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Humans
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • Smad4 Protein / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Biomarkers
  • SMAD4 protein, human
  • Smad4 Protein
  • MIRN204 microRNA, human