Cai Shang, Li Ya, Bai Jin-Yu, Zhang Zhi-Qing, Wang Yin, Qiao Yin-Biao, Zhou Xiao-Zhong, Yang Bo, Tian Ye, Cao Cong
Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Neuroscience, Soochow University, Suzhou, China.
Oncotarget. 2017 May 23;8(21):35061-35068. doi: 10.18632/oncotarget.17043.
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.
我们之前已经表明，Gαi3在人类胶质瘤中表达上调，介导Akt激活和癌细胞增殖。在此，我们认为Gαi3对于辐射抗性也可能很重要。在A172人类胶质瘤细胞中，Gαi3敲低（通过靶向短发夹RNA）或显性负性突变显著增强了辐射诱导的细胞凋亡。相反，野生型或组成型活性Gαi3的强制过表达抑制了辐射诱导的A172细胞凋亡。A172细胞中的辐射诱导Gαi3易位至细胞核，并与局部蛋白DNA依赖性蛋白激酶（DNA-PK）催化亚基结合。这种结合对于DNA损伤修复很重要。Gαi3敲低、缺失（使用Gαi3基因敲除的小鼠胚胎成纤维细胞）或显性负性突变增强了辐射诱导的DNA损伤。另一方面，组成型活性Gαi3在A172细胞中的表达抑制了辐射引起的DNA损伤。总之，这些结果表明Gαi3在人类胶质瘤细胞的辐射抗性中具有新功能。
