Sp1 contributes to radioresistance of cervical cancer through targeting G2/M cell cycle checkpoint CDK1
Authors Deng YR, Chen XJ, Chen W, Wu LF, Jiang HP, Lin D, Wang LJ, Wang W, Guo SQ
Received 9 January 2019
Accepted for publication 21 May 2019
Published 28 June 2019 Volume 2019:11 Pages 5835—5844
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Professor Nakshatri
Yuan-Run Deng,1* Xiao-Jing Chen,2* Wei Chen,1 Lan-Fang Wu,1 Hui-Ping Jiang,1 Dan Lin,1 Li-Jing Wang,1 Wei Wang*,2,3 Sui-Qun Guo1,
1Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
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.
Keywords: cervical cancer, Sp1, radioresistance, G2/M phase, CDK1
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