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Sp1 contributes to radioresistance of cervical cancer through targeting G2/M cell cycle checkpoint CDK1
| Content Provider | Scilit |
|---|---|
| Author | Deng, Yuan-Run Chen, Xiao-Jing Chen, Wei Wu, Lan-Fang Jiang, Hui-Ping Lin, Dan Wang, Li-Jing Wang, Wei Guo, Sui-Qun |
| Copyright Year | 2019 |
| Description | Background/aims: Radioresistance remains a significant obstacle in the therapy of cervical cancer, and the mechanism of it is still unclear. We aimed to investigate the role of specificity protein 1 (Sp1) in radioresistance of cervical cancer. Methods: Sp1 was examined immunohistochemically on tissues from 36 human cervical cancer patients. We used RT-qPCR and Western blot to examine the expression of Sp1 in irradiated cervical cancer cell lines SiHa and HeLa. The role of Sp1 in radioresistance of cervical cancer cells was assessed by colony-formation assay and cell cycle analysis. Dual-luciferase reporter assay was performed to detect the downstream of Sp1. Results: High Sp1 expression was positively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and lymphovascular space invasion (LVSI) of cervical cancer. The expression of Sp1 was dose-dependently increased in irradiated cervical cancer cell lines at both mRNA and protein levels. Colony-formation assay showed that alteration of Sp1 expression affected the survival of cervical cancer cells with radiotherapy (RT) treatment. Knockdown of Sp1 significantly strengthened the cellular response to radiation by inducing G2/M arrest in cervical cancer cells. Overexpression of Sp1 significantly decreased G2/M arrest in cervical cancer cells, which was related to upregulation of CDK1 expression. Dual-luciferase reporter assay showed the direct effect of Sp1 on the transcriptional activation of CDK1. Conclusion: Sp1 may contribute to radioresistance through inhibiting G2/M phase arrest by targeting CDK1, and be considered as a potential therapeutic target to promote the effect of RT for patients with cervical cancer. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610296/pdf https://www.dovepress.com/getfile.php?fileID=50788 |
| Ending Page | 5844 |
| Page Count | 10 |
| Starting Page | 5835 |
| ISSN | 11791322 |
| DOI | 10.2147/cmar.s200907 |
| Journal | Cancer Management and Research |
| Volume Number | 11 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2019-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Management and Research Oncology Cdk1 G2/m Phase Sp1 Cervical Cancer Radioresistance |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |