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Knockdown of TNF receptor-associated factor 2 (TRAF2) modulates in vitro growth of TRAIL-treated prostate cancer

Bingbing Wei1, Jun Ruan2, Yuanyuan Mi1

  • 1Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|July 2, 2017
PubMed

Insights

Tumor necrosis factor receptor-associated factor 2 (TRAF2) influences androgen-refractory prostate cancer growth by regulating SIRT1. TRAF2 may serve as a biomarker for predicting recurrence-free survival in prostate cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays a role in tumor development.
  • The specific impact of TRAF2 on androgen-refractory prostate cancer growth and its underlying mechanisms, particularly in response to TRAIL (TNF-related apoptosis-inducing ligand), remain unclear.

Purpose of the Study:

  • To investigate the effect of TRAF2 on the in vitro growth of human androgen-insensitive prostate cancer DU-145 cells when treated with TRAIL.
  • To explore the molecular mechanisms by which TRAF2 influences prostate cancer growth and survival.

Main Methods:

  • Bioinformatics analysis of TCGA and GEO (GSE21032) datasets to assess TRAF2 expression and its prognostic value in prostate cancer.
  • In vitro assays including colony formation, cell viability, and apoptosis (Annexin V/PI staining) to evaluate TRAF2's impact on DU-145 cells treated with TRAIL.
  • Quantitative RT-PCR and immunoblotting to measure mRNA and protein expression levels of TRAF2 and SIRT1.

Main Results:

  • TRAF2 expression is significantly upregulated in prostate cancer patients with higher Gleason scores (GS>7) and is associated with recurrence-free survival.
  • TRAF2 knockdown enhances apoptosis and downregulates SIRT1 expression in TRAIL-treated DU-145 cells.
  • SIRT1 knockdown inhibits growth and promotes apoptosis in TRAIL-treated DU-145 cells, indicating its role in TRAF2-mediated effects.

Conclusions:

  • TRAF2 influences the in vitro growth of TRAIL-treated androgen-insensitive prostate cancer cells, at least partially through the regulation of SIRT1 expression.
  • TRAF2 may serve as a valuable biomarker for predicting recurrence-free survival in prostate cancer patients.
Keywords:
TRAF2TRAILproliferationprostate cancer

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