RNA over-editing of BLCAP contributes to hepatocarcinogenesis identified by whole-genome and transcriptome sequencing

Cancer Lett. 2015 Feb 28;357(2):510-9. doi: 10.1016/j.canlet.2014.12.006. Epub 2014 Dec 8.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, although the treatment of this disease has changed little in recent decades because most of the genetic events that initiate this disease remain unknown. To better understand HCC pathogenesis at the molecular level and to uncover novel tumor-initiating events, we integrated RNA-seq and DNA-seq data derived from two pairs of HCC tissues. We found that BLCAP is novel editing gene in HCC and has over-editing expression in 40.1% HCCs compared to adjacent liver tissues. We then used RNA interference and gene transfection to assess the roles of BLCAP RNA editing in tumor proliferation. Our results showed that compared to the wild-type BLCAP gene, the RNA-edited BLCAP gene may stably promote cell proliferation (including cell growth, colony formation in vitro, and tumorigenicity in vivo) by enhancing the phosphorylation of AKT, mTOR, and MDM2 and inhibiting the phosphorylation of TP53. Our current results suggest that the RNA over-editing of BLCAP gene may serve as a novel potential driver in advanced HCC through activating AKT/mTOR signal pathway.

Keywords: BLCAP gene; Hepatocarcinogenesis; RNA over-editing; Whole-genome and transcriptome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Genome, Human / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Male
  • Mice, Nude
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • RNA Editing*
  • RNA Interference
  • Sequence Analysis / methods
  • TOR Serine-Threonine Kinases / metabolism
  • Transcriptome / genetics*
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BLCAP protein, human
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-mdm2
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt