The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation

Cell Death Dis. 2021 Apr 6;12(4):351. doi: 10.1038/s41419-021-03595-x.

Abstract

Aberrant long-noncoding RNA (lncRNA) expression has been shown to be involved in the pathogenesis of endometrial cancer (EC). Herein, we report a novel tumor suppressor lncRNA SOCS2-AS1 in EC. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nuclear/cytoplasmic fractionation assays were used to detect the subcellular location. We found that SOCS2-AS1 was downregulated in EC tissues. Its reduced expression was correlated with advanced clinical stage and poor prognosis. Forced expression of SOCS2-AS1 suppressed EC cell proliferation and induced cell-cycle arrest and apoptosis. SOCS2-AS1-binding proteins were detected using RNA pull-down assay and mass spectrometry. Mechanistically, SOCS2-AS1 bound to Aurora kinase A (AURKA) and increased its degradation through the ubiquitin-proteasome pathway. In conclusion, SOCS2-AS1 may thus serve as a prognostic predictor and a biomarker for AURKA-inhibitor treatment in EC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Aurora Kinase A / genetics*
  • Aurora Kinase A / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Down-Regulation
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor / physiology
  • Humans
  • MicroRNAs / genetics
  • RNA, Long Noncoding / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • SOCS2 protein, human
  • Suppressor of Cytokine Signaling Proteins
  • AURKA protein, human
  • Aurora Kinase A