Obstetrics and Gynecology Department, The Affiliated Zhangjiagang Hospital of Soochow University, Institute of Neuroscience, Soochow University, Suzhou, China.
Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Soochow University, Suzhou, China.
Int J Biol Sci. 2022 Sep 6;18(15):5667-5680. doi: 10.7150/ijbs.77126. eCollection 2022.
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. , 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.
在这里，我们研究了 Gαi3 在宫颈癌中的表达和潜在功能。生物信息学分析以及对当地患者组织的研究结果表明，Gαi3 在人宫颈癌组织和不同的宫颈癌细胞中表达显著升高，并与患者的总生存不良和疾病特异性生存不良相关。Gαi3 的耗竭导致了显著的抗宫颈癌活性。在原代或永生化的宫颈癌细胞中，Gαi3 shRNA 或 CRISPR/Cas9 引起的 Gαi3 敲除/KO 极大地阻碍了细胞增殖和迁移，并引发了细胞凋亡。相比之下，外源性 Gαi3 过表达进一步增强了宫颈癌的增殖和迁移。Gαi3 沉默或 KO 后，原代宫颈癌细胞中的 Akt-mTOR 激活显著降低，但 Gαi3 过表达后则增强。进一步的研究表明，转录因子 GATA4 与宫颈癌组织和细胞中 Gαi3 启动子区域的结合显著增强。GATA4 shRNA 可降低 Gαi3 的表达，但 GATA4 过表达后则上调 Gαi3 的表达。Gαi3 沉默或 KO 后，宫颈癌异种移植的生长受到强烈抑制。在 Gαi3 沉默/-KO 宫颈癌异种移植组织中检测到 Gαi3 耗竭和 Akt-mTOR 失活。总之，上调的 Gαi3 是宫颈癌有价值的致癌靶点。
