Long noncoding RNA PCAT-14 induces proliferation and invasion by hepatocellular carcinoma cells by inducing methylation of miR-372

Oncotarget. 2017 May 23;8(21):34429-34441. doi: 10.18632/oncotarget.16260.

Abstract

Long non-coding RNAs (lncRNAs) regulate oncogenesis by inducing methylation of CpG islands to silence target genes. Here we show that the lncRNA PCAT-14 is overexpressed in patients with hepatocellular carcinoma (HCC), and is associated with a poor prognosis after surgery. Our results demonstrate that PCAT-14 promotes proliferation, invasion, and cell cycle arrest in HCC cells. In addition, PCAT-14 inhibits miR-372 expression by inducing methylation of the miR-372 promoter. Simultaneously, miR-372 eliminates the effects of PCAT-14 on proliferation, invasion, and cell cycle in HCC cells. Moreover, PCAT-14 regulates expression of ATAD2 and activation of the Hedgehog pathway via miR-372. These findings indicate that PCAT-14 plays an important role in HCC, and may serve as a novel prognostic factor and therapeutic target.

Keywords: HCC; PCAT-14; invasion; miR-372; proliferation.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics*
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Survival Analysis
  • Tumor Burden
  • Up-Regulation*

Substances

  • DNA-Binding Proteins
  • MIRN372 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA PCAT-14, human
  • ATAD2 protein, human
  • ATPases Associated with Diverse Cellular Activities