Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis

Tumour Biol. 2017 Mar;39(3):1010428317694572. doi: 10.1177/1010428317694572.

Abstract

Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response. However, the functions of p53-inducible gene 3(PIG3) in cancer are far from clear including glioblastoma. In this study, we found that p53-inducible gene 3 expression was suppressed in glioblastoma tissues compared with normal tissues. And the expression of p53-inducible gene 3 was significantly associated with the World Health Organization grade. Patients with high p53-inducible gene 3 expression have a significantly longer median survival time (15 months) than those with low p53-inducible gene 3 expression (8 months). According to Cox regression analysis, p53-inducible gene 3 was an independent prognostic factor with multivariate hazard ratio of 0.578 (95% confidence interval, 0.352-0.947; p = 0.030) for overall survival. Additionally, gain and loss of function experiments showed that knockdown of p53-inducible gene 3 significantly increased the proliferation and invasion ability of glioblastoma cells while overexpression of p53-inducible gene 3 inhibited the proliferation and invasion ability. The results of in vivo glioblastoma models further confirmed that p53-inducible gene 3 suppression promoted glioblastoma progression. Altogether, our data suggest that high expression of p53-inducible gene 3 is significant for glioblastoma inhibition and p53-inducible gene 3 independently indicates good prognosis in patients, which might be a novel prognostic biomarker or potential therapeutic target in glioblastoma.

Keywords: glioblastoma; invasion; p53-inducible gene 3; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Cell Proliferation / genetics
  • Child
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioblastoma / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Middle Aged
  • Prognosis*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • TP53I3 protein, human
  • Tumor Suppressor Protein p53