LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway

Oncotarget. 2015 Dec 15;6(40):42813-24. doi: 10.18632/oncotarget.5970.

Abstract

Hepatocellular carcinoma (HCC) is well known as the sixth most common malignant tumor and the third leading cause of cancer-related deaths globally. LINC00152 was documented as an important long non-coding RNA (lncRNA) involved in the pathogenesis of gastric cancer; however, the detailed mechanism of action of LINC00152 remains unknown. Here, based on the increased level of LINC00152 in HCC tissues, we found that LINC00152 could promote cell proliferation in vitro and tumor growth in vivo. Furthermore, microarray-based analysis indicated that LINC00152 could activate the mechanistic target of rapamycin(mTOR) pathway by binding to the promoter of EpCAM through a cis-regulation, as confirmed by Gal4-λN/BoxB reporter system. Thus, LINC00152 might be involved in the oncogenesis of HCC by activating the mTOR signaling pathway and might be a novel index for clinical diagnosis in the future.

Keywords: EpCAM; HCC; lncRNA; mTOR; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Proliferation* / genetics
  • Cell Transformation, Neoplastic / genetics
  • Chromatin Immunoprecipitation
  • Epithelial Cell Adhesion Molecule
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • long non-coding RNA Linc00152, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases