Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma

Oncotarget. 2015 Mar 20;6(8):5666-77. doi: 10.18632/oncotarget.3290.


The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies - include growth curves, cell death, migration assays and in vivo studies - verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.

Keywords: INTS6; competitive endogenous RNA; hepatocellular carcinoma; pseudogene; tumor suppressor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Genes, Tumor Suppressor
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Pseudogenes*
  • RNA-Binding Proteins
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Transfection
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism


  • INTS6 protein, human
  • MIRN17 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • Tumor Suppressor Proteins