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

Oncotarget
Yizhou QuanWei-Qiang Gao

Abstract

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.

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Methods Mentioned

BETA
ubiquitination
Immunoprecipitation
PCR
transfection
Assay

Software Mentioned

GraphPad Prism
Adobe Photoshop
Oncomine

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