PARP6 acts as a tumor suppressor via downregulating Survivin expression in colorectal cancer

Oncotarget. 2016 Apr 5;7(14):18812-24. doi: 10.18632/oncotarget.7712.

Abstract

Poly (ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and are involved in a variety of biological processes. PARP6 is a novel member, and our previous findings suggest that PARP6 may act as a tumor suppressor via suppressing cell cycle progression. However, it is still unclear that PARP6 function besides growth suppression in colorectal cancer (CRC). In this study, we examined tumor suppressive roles of PAPR6 in CRC cells both in vitro and in vivo. We found that PARP6 inhibited colony formation, invasion and migration as well as cell proliferation. Moreover, ectopic overexpression of PARP6 decreased Survivin expression, which acts as an oncogene and is involved in apoptosis and mitosis. We confirmed the inverse correlation between PARP6 and Survivin expression in CRC cases by immunohistochemistry. Importantly, CRC cases with downregulation of PARP6 and upregulation of Survivin showed poor prognosis. In summary, PARP6 acts as a tumor suppressor via downregulating Survivin expression in CRC. PARP6 can be a novel diagnostic and therapeutic target together with Survivin for CRC.

Keywords: PARP6; Survivin; colorectal cancer; prognosis; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / genetics*
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Male
  • Signal Transduction
  • Survivin

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Survivin
  • ADP Ribose Transferases
  • PARP6 protein, human