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

Abstract

Here we studied expression and potential functions of Gαi3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that Gαi3 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. Gαi3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, Gαi3 shRNA or CRISPR/Cas9-caused Gαi3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic Gαi3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after Gαi3 silencing or KO, but was augmented following Gαi3 overexpression. Further studies revealed that the transcription factor GATA4 binding to Gαi3 promoter region was significantly enhanced in cervical cancer tissues and cells. Gαi3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo, the growth of cervical cancer xenografts was robustly suppressed after Gαi3 silencing or KO. Gαi3 depletion and Akt-mTOR inactivation were detected in Gαi3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated Gαi3 is a valuable oncotarget of cervical cancer.

• Authors: Jie Zhang, De-Pei Yin, Yan Zhang, Jia-Nan Zhang, Yan Yang, Zhi-Qing Zhang, Li Zhou, Yan Lv, Hai-Wei Huang, Cong Cao
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 18 Issue 15 Pg. 5667-5680 ( 2022) ISSN: 1449-2288 [Electronic] Australia
• PMID: 36263185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Proto-Oncogene Proteins c-akt
• GATA4 Transcription Factor
• RNA, Small Interfering
• TOR Serine-Threonine Kinases

Topics

• Female
• Humans
• Proto-Oncogene Proteins c-akt (metabolism)
• GATA4 Transcription Factor
• RNA, Small Interfering (genetics)
• Uterine Cervical Neoplasms (genetics, metabolism)
• Cell Proliferation (genetics)
• TOR Serine-Threonine Kinases (metabolism)
• Apoptosis (genetics)
• Cell Line, Tumor