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

Zhang, Jie; Yin, De-pei; Zhang, Yan; Zhang, Jia-nan; Yang, Yan; Zhang, Zhi-qing; Zhou, Li; Lv, Yan; Huang, Hai-wei; Cao, Cong

doi:10.7150/ijbs.77126

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Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

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Int J Biol Sci 2022; 18(15):5667-5680. doi:10.7150/ijbs.77126 This issue Cite

Research Paper

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

Jie Zhang^1#, De-pei Yin^2#, Yan Zhang^3#, Jia-nan Zhang^1#, Yan Yang¹, Zhi-qing Zhang¹, Li Zhou⁴, Yan Lv^4✉, Hai-wei Huang^1✉, Cong Cao^1✉

1. Obstetrics and Gynecology Department, The Affiliated Zhangjiagang Hospital of Soochow University, Institute of Neuroscience, Soochow University, Suzhou, China.
2. Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Soochow University, Suzhou, China.
3. Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China.
4. Center of Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.
#Equal contribution

Citation:

Zhang J, Yin Dp, Zhang Y, Zhang Jn, Yang Y, Zhang Zq, Zhou L, Lv Y, Huang Hw, Cao C. Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer. Int J Biol Sci 2022; 18(15):5667-5680. doi:10.7150/ijbs.77126. https://www.ijbs.com/v18p5667.htm

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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.

Keywords: Cervical cancer, Targeted therapy, Gαi3, Akt-mTOR

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APA

Zhang, J., Yin, D.p., Zhang, Y., Zhang, J.n., Yang, Y., Zhang, Z.q., Zhou, L., Lv, Y., Huang, H.w., Cao, C. (2022). Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer. International Journal of Biological Sciences, 18(15), 5667-5680. https://doi.org/10.7150/ijbs.77126.

ACS

Zhang, J.; Yin, D.p.; Zhang, Y.; Zhang, J.n.; Yang, Y.; Zhang, Z.q.; Zhou, L.; Lv, Y.; Huang, H.w.; Cao, C. Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer. Int. J. Biol. Sci. 2022, 18 (15), 5667-5680. DOI: 10.7150/ijbs.77126.

NLM

CSE

Zhang J, Yin Dp, Zhang Y, Zhang Jn, Yang Y, Zhang Zq, Zhou L, Lv Y, Huang Hw, Cao C. 2022. Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer. Int J Biol Sci. 18(15):5667-5680.

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