LncRNA-ZXF1 stabilizes P21 expression in endometrioid endometrial carcinoma by inhibiting ubiquitination-mediated degradation and regulating the miR-378a-3p/PCDHA3 axis

Mol Oncol. 2022 Feb;16(3):813-829. doi: 10.1002/1878-0261.12940. Epub 2021 Mar 22.

Abstract

Long noncoding RNAs (lncRNAs) have a profound effect on biological processes in various malignancies. However, few studies have investigated their functions and specific mechanisms in endometrial cancer. In this study, we focused on the role and mechanism of lncRNA-ZXF1 in endometrial cancer. Bioinformatics and in vitro and in vivo experiments were used to explore the expression and function of lncRNA-ZXF1. We found that lncRNA-ZXF1 altered the migration and invasion of endometrioid endometrial cancer (EEC) cells. Furthermore, our results suggest that lncRNA-ZXF1 regulates EEC cell proliferation. This regulation may be achieved by the lncRNA-ZXF1-mediated alteration in the expression of P21 through two mechanisms. One is that lncRNA-ZXF1 functions as a molecular sponge of miR-378a-3p to regulate PCDHA3 expression and then modulate the expression of P21. The other is that lncRNA-ZXF1 inhibits CDC20-mediated degradation of ubiquitination by directly binding to P21. To the best of our knowledge, this study is the first to explore lncRNA-ZXF1 functioning as a tumor-suppressing lncRNA in EEC. LncRNA-ZXF1 may become therapeutic, diagnostic, and prognostic indicator in the future.

Keywords: P21; cell cycle; endometrioid endometrial cancer; lncRNA-ZXF1; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Endometrial Neoplasms* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Ubiquitination / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding