Oncotarget

Research Papers:

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

Yizhou Quan, Naitao Wang, Qianqian Chen, Jin Xu, Wei Cheng, Meijuan Di, Weiliang Xia and Wei-Qiang Gao _

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Oncotarget. 2015; 6:26494-26507. https://doi.org/10.18632/oncotarget.4764

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Abstract

Yizhou Quan1, Naitao Wang1, Qianqian Chen1, Jin Xu1, Wei Cheng2, Meijuan Di3, Weiliang Xia1 and Wei-Qiang Gao1,4

1 State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

2 Department of Urology, First People’s Hospital of Xiaoshan, Hangzhou, Zhejiang, China

3 Department of Pathology, First People’s Hospital of Xiaoshan, Hangzhou, Zhejiang, China

4 Collaborative Innovation Center of Systems Biomedicine, Shanghai, China

Correspondence to:

Weiliang Xia, email:

Wei-Qiang Gao, email:

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

Received: March 23, 2015 Accepted: June 25, 2015 Published: July 03, 2015

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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