SIRT3 inhibits prostate cancer by destabilizing oncoprotein c-MYC through regulation of the PI3K/Akt pathway

Oncotarget. 2015 Sep 22;6(28):26494-507. doi: 10.18632/oncotarget.4764.


SIRT3 is involved in aging-related diseases including cancer, but its role in prostate cancer and detailed regulatory function are not known. We found that SIRT3 was moderately down-regulated in prostate carcinomas. Overexpression of SIRT3 by lentiviral transfection inhibited prostate cancer growth both in vitro and in vivo, whereas knockdown of SIRT3 increased prostate tumor growth. Mechanistically, the tumor suppression effect of SIRT3 was achieved via its inhibition of the PI3K/Akt pathway. Notably, upregulation of SIRT3 suppressed the phosphorylation of Akt, leading to the ubiquitination and degradation of oncoprotein c-MYC; this could be attenuated by constitutive activation of PI3K/Akt signaling. Collectively, our results unveiled SIRT3's tumor suppressive function and the underlying mechanism in prostate cancer, which might provide therapeutic implications for the disease.

Keywords: PI3K-Akt pathway; SIRT3; c-MYC; oncoprotein; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphorylation
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Protein Stability
  • Proteolysis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA Interference
  • Signal Transduction
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*
  • Time Factors
  • Transfection
  • Ubiquitination


  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • SIRT3 protein, human
  • Sirtuin 3