Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer

Here we studied expression and potential functions of G alpha i3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that G alpha i3 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. G alpha i3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, G alpha i3 shRNA or CRISPR/Cas9-caused G alpha i3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic G alpha i3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after G alpha i3 silencing or KO, but was augmented following G alpha i3 overexpression. Further studies revealed that the transcription factor GATA4 binding to G alpha i3 promoter region was significantly enhanced in cervical cancer tissues and cells. G alpha i3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo, the growth of cervical cancer xenografts was robustly suppressed after G alpha i3 silencing or KO. G alpha i3 depletion and Akt-mTOR inactivation were detected in G alpha i3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated G alpha i3 is a valuable oncotarget of cervical cancer.

Automated summary

This study found that the expression of G alpha i3 is significantly increased in cervical cancer, and it is associated with poor survival in patients. Depletion of G alpha i3 has anti-cervical cancer activity, while overexpression promotes cervical cancer proliferation and migration. The binding of GATA4 to the promoter region of G alpha i3 is enhanced in cervical cancer. The results indicate that G alpha i3 could be a potential therapeutic target for cervical cancer.