Oncotarget

Research Papers:

Loss of PIG3 increases HIF-1α level by promoting protein synthesis via mTOR pathway in renal cell carcinoma cells

Guang Chen, Jin-Ye Xu, Jie Chen, Jian-Xin Zhang, Jun Zhou, Yong Liang and Xiao-Fei Ding _

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Oncotarget. 2016; 7:27176-27184. https://doi.org/10.18632/oncotarget.8401

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Abstract

Guang Chen1,2,*, Jin-Ye Xu3,4,*, Jie Chen5, Jian-Xin Zhang5, Jun Zhou5, Yong Liang4,5 and Xiao-Fei Ding5

1 School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou, Zhejiang, China

2 Institute of Tumor, Taizhou University, Taizhou, Zhejiang, China

3 Laboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China

4 Taizhou Municipal Hospital, Taizhou, Zhejiang, China

5 School of Medicine, Taizhou University, Taizhou, Zhejiang, China

* These authors have contributted equally to this work

Correspondence to:

Xiao-Fei Ding, email:

Keywords: PIG3, HIF-1α, mTOR, renal cell carcinoma, migration

Received: August 24, 2015 Accepted: March 16, 2016 Published: March 27, 2016

Abstract

PIG3 is a target of the tumor suppressor p53 and is thought to be involved in p53-mediated cell apoptosis. Although PIG3 is similar to oxidoreductases involved in generating ROS, whether PIG3 would regulate HIF-1α was never characterized directly. Here we demonstrated that knockdown of PIG3 by transfecting with specific siRNA could increase the expression of HIF-1α in several human cancer cell lines, including CAKI, FTC-133 and A549. It indicates that PIG3 may be involved in the regulation of HIF-1α. Furthermore, we revealed that PIG3-siliencing increased HIF-1α protein level through promoting its protein biosynthesis via mTOR pathway. In addition, the effect of PIG3 on the production of HIF-1α was further related to VEGF secretion and cell migration. PIG3-downregulation increased the secretion of VEGF and promoted the migration of renal cancer cells obviously. Taken together, these data suggest that PIG3 was involved in HIF-1α regulation, and reveal a novel signaling pathway of PIG3/HIF-1α in the regulation of cell migration in renal cell carcinoma.


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