Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer
Jie Zhang, De-Pei Yin, Yan Zhang, Jia-nan Zhang, Yan Yang, Zhi-qing Zhang, Li Zhou, Yan Lv, Haiwei Huang, Cong Cao
Abstract
Here we studied expression and potential functions of Gi3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that Gi3 expression was remarkably elevated in human cervical cancer tissues and different cervical cancer cells, and was associated with poor overall survival and poor disease-specific survival of patients. Gi3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, Gi3 shRNA or CRISPR/Cas9-caused Gi3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic Gi3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after Gi3 silencing or KO, but was augmented following Gi3 overexpression. Further studies revealed that the transcription factor GATA4 binding to Gi3 promoter region was significantly enhanced in cervical cancer tissues and cells. Gi3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo, the growth of cervical cancer xenografts was robustly suppressed after Gi3 silencing or KO. Gi3 depletion and Akt-mTOR inactivation were detected in Gi3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated Gi3 is a valuable oncotarget of cervical cancer.