Gαi3 nuclear translocation causes irradiation resistance in human glioma cells

Shang Cai; Ya Li; Jin-Yu Bai; Zhi-Qing Zhang; Yin Wang; Yin-Biao Qiao; Xiao-Zhong Zhou; Bo Yang; Ye Tian; Cong Cao

doi:10.18632/oncotarget.17043

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Research Papers:

Gαi3 nuclear translocation causes irradiation resistance in human glioma cells

Shang Cai, Ya Li, Jin-Yu Bai, Zhi-Qing Zhang, Yin Wang, Yin-Biao Qiao, Xiao-Zhong Zhou, Bo Yang, Ye Tian and Cong Cao _

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Oncotarget. 2017; 8:35061-35068. https://doi.org/10.18632/oncotarget.17043

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Abstract

Shang Cai1,*, Ya Li2,*, Jin-Yu Bai3,*, Zhi-Qing Zhang2,*, Yin Wang2, Yin-Biao Qiao4, Xiao-Zhong Zhou3, Bo Yang4, Ye Tian1, Cong Cao2

1Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China

2Institute of Neuroscience, Soochow University, Suzhou, China

3Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China

4Department of Surgery, The Third Hospital affiliated to Soochow University, Suzhou, China

*Co-first authors

Correspondence to:

Bo Yang, email: [email protected]

Ye Tian, email: [email protected], [email protected]

Cong Cao, email: [email protected]

Keywords: glioma, irradiation, Gαi3, DNA-PKcs

Received: March 13, 2017 Accepted: March 30, 2017 Published: April 11, 2017

ABSTRACT

We have previously shown that Gαi3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gαi3 could also be important for irradiation resistance. In A172 human glioma cells, Gαi3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gαi3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gαi3 translocation to cell nuclei and association with local protein DNA-dependent protein kinase (DNA-PK) catalytic subunit. This association was important for DNA damage repair. Gαi3 knockdown, depletion (using Gαi3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gαi3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gαi3 in irradiation-resistance in human glioma cells.

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Research Papers:

Gαi3 nuclear translocation causes irradiation resistance in human glioma cells

Abstract