Long noncoding RNA DARS-AS1 regulates TP53 ubiquitination and affects ovarian cancer progression by modulation miR-194-5p/RBX1 axis

J Biochem Mol Toxicol. 2021 Oct;35(10):e22865. doi: 10.1002/jbt.22865. Epub 2021 Jul 30.

Abstract

Background: Ovarian cancer is a malignant tumor with a poor prognosis, its underlying mechanism is still unclear.

Objective: In this study, long noncoding RNA DARS-AS1 was studied to identify its function in the development of ovarian cancer.

Methods: Perform functional experiments to detect the effects of DARS-AS1 on the proliferation, apoptosis, and migration of ovarian cancer cells A2780. The luciferase report, immunoprecipitation (IP) experiment, and ubiquitination level determination verify that RBX1 ubiquitination and mediate the degradation of tumor suppressor gene TP53.

Results: Knockdown of DARS-AS1 can inhibit cell proliferation, migration, and apoptosis, and the application of miR-194-5p inhibitors can prevent this process. Luciferase and IP experiments showed that DARS-AS1 regulates the expression of RBX1 by binding to miR-194-5p, and RBX1 mediates its degradation through ubiquitination of TP53.

Keywords: DARS-AS1; RBX1; TP53; miR-194-5p; ovarian cancer.

MeSH terms

  • Apoptosis / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • Female
  • Gene Knockdown Techniques / methods
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / genetics*
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitination / genetics*

Substances

  • Carrier Proteins
  • MIRN194 microRNA, human
  • MicroRNAs
  • RBX1 protein, human
  • RNA, Antisense
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53