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

Haoran Peng, Masaharu Ishida, Ling Li, Atsushi Saito, Atsushi Kamiya, James P. Hamilton, Rongdang Fu, Alexandru V. Olaru, Fangmei An, Irinel Popescu, Razvan Iacob, Simona Dima, Sorin T. Alexandrescu, Razvan Grigorie, Anca Nastase, Ioana Berindan-Neagoe, Ciprian Tomuleasa, Florin Graur, Florin Zaharia, Michael S. TorbensonEsteban Mezey, Minqiang Lu, Florin M. Selaru

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5666-5677
Number of pages12
JournalOncotarget
Volume6
Issue number8
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Competitive endogenous RNA
  • Hepatocellular carcinoma
  • INTS6
  • Pseudogene
  • Tumor suppressor

ASJC Scopus subject areas

  • Oncology

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    Peng, H., Ishida, M., Li, L., Saito, A., Kamiya, A., Hamilton, J. P., Fu, R., Olaru, A. V., An, F., Popescu, I., Iacob, R., Dima, S., Alexandrescu, S. T., Grigorie, R., Nastase, A., Berindan-Neagoe, I., Tomuleasa, C., Graur, F., Zaharia, F., ... Selaru, F. M. (2015). Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma. Oncotarget, 6(8), 5666-5677. https://doi.org/10.18632/oncotarget.3290