UNC5B-AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2

Cell Biol Int. 2020 Apr;44(4):1028-1036. doi: 10.1002/cbin.11300. Epub 2020 Jan 21.

Abstract

The role of long non-coding RNAs (lncRNAs) in tumorigenesis and development of ovarian cancer (OC) has caught the attention of scientists. UNC5B antisense RNA 1 (UNC5B-AS1) is a newly identified carcinogenic lncRNA in thyroid papillary carcinoma, but its role in OC remains unclear. This study is proposed to investigate the function and mechanism of UNC5B-AS1 in OC. UNC5B-AS1 expression in OC samples was obtained from gene expression profiling interactive analysis (GEPIA) based on The Cancer Genome Atlas data. Gene expressions were detected by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. Biological functions of UNC5B-AS1 were assessed by cell counting kit-8, colony formation, and caspase-3 analysis. GEPIA revealed the UNC5B-AS1 upregulation in OC samples. RT-qPCR assay confirmed the upregulation of UNC5B-AS1 in OC cells. Functionally, depletion of UCN5B-AS1 hindered proliferation and prompted apoptosis in OC cells. Mechanistically, we found that UNC5B-AS1 interacted with zeste 2 polycomb repressive complex 2 subunit (EZH2) to trigger trimethylation of histone H3 at lysine 27 (H3K27me3) on N-myc downstream regulated gene-2 (NDRG2) promoter and epigenetically repressed NDRG2. Rescue assay indicated the participation of NDRG2 in the regulation of UNC5B-AS1 on OC progression. Together, we first illustrated that UNC5B-AS1 promoted OC progression by regulating the H3K27me on NDRG2 via EZH2, indicating UNC5B-AS1 as a potential molecular target for OC treatment.

Keywords: EZH2; H3K27me; NDRG2; UNC5B-AS1; ovarian cancer.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Female
  • Humans
  • Netrin Receptors / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • RNA, Antisense / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • NDRG2 protein, human
  • Netrin Receptors
  • RNA, Antisense
  • Tumor Suppressor Proteins
  • UNC5B protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein