Ataxin-3 promotes testicular cancer cell proliferation by inhibiting anti-oncogene PTEN

Biochem Biophys Res Commun. 2018 Sep 3;503(1):391-396. doi: 10.1016/j.bbrc.2018.06.047. Epub 2018 Jun 18.

Abstract

Human Ataxin-3 protein was first identified as a transcript from patients with Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3). Recent studies have demonstrated that Ataxin-3 is involved in gastric cancer and lung cancer. However, the role of Ataxin-3 in testicular cancer (TC) remains poorly understood. This study aims to explore the significance of Ataxin-3 expression in TC. Firstly, we investigated 53 paired TC and para-tumor tissues and found that Ataxin-3 was overexpressed in TC tissues, and this overexpression of Ataxin-3 was correlated with tumor stages. Functionally, Ataxin-3 overexpression promoted cell proliferation, and Ataxin-3 knockdown inhibited cell proliferation. In addition, up-regulation of Ataxin-3 inhibited the expression of PTEN and activated the AKT/mTOR pathway. Conversely, inhibition of Ataxin-3 suppressed the expression of p-AKT and p-mTOR, and increased the expression of p-4EBP1. These findings may provide a better understanding about the mechanism of TC and suggest that Ataxin-3 may be a potential prognostic biomarker and therapeutic target for TC.

Keywords: AKT/mTOR signaling; Ataxin-3; Cell proliferation; PTEN; Testicular cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3 / genetics*
  • Ataxin-3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • PTEN Phosphohydrolase / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / pathology*
  • Testis / metabolism
  • Testis / pathology

Substances

  • Repressor Proteins
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • ATXN3 protein, human
  • Ataxin-3