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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
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Sp1 contributes to radioresistance of cervical cancer through targeting G2/M cell cycle checkpoint CDK1

Yuan-Run Deng1, Xiao-Jing Chen2, Wei Chen1

  • 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

Cancer Management and Research
|July 16, 2019
PubMed
Abstract

Insights

Specificity protein 1 (Sp1) promotes cervical cancer radioresistance by inhibiting G2/M arrest via CDK1. Targeting Sp1 could enhance radiotherapy effectiveness in cervical cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Radioresistance is a major challenge in cervical cancer treatment.
  • The underlying mechanisms of radioresistance in cervical cancer are not fully understood.
  • Specificity protein 1 (Sp1) is investigated for its potential role in cervical cancer radioresistance.

Purpose of the Study:

  • To investigate the role of Sp1 in the radioresistance of cervical cancer.
  • To determine the correlation between Sp1 expression and clinical parameters in cervical cancer.
  • To elucidate the molecular mechanism by which Sp1 influences cervical cancer cell response to radiotherapy.

Main Methods:

  • Immunohistochemistry was used to assess Sp1 expression in 36 human cervical cancer tissues.
  • RT-qPCR and Western blot analyzed Sp1 expression in irradiated SiHa and HeLa cell lines.
  • Colony-formation assays, cell cycle analysis, and dual-luciferase reporter assays were employed to evaluate Sp1 function and its downstream targets.

Main Results:

  • High Sp1 expression correlated with advanced FIGO stage, lymph node metastasis, and lymphovascular space invasion (LVSI).
  • Sp1 expression increased dose-dependently in irradiated cervical cancer cells at both mRNA and protein levels.
  • Sp1 knockdown enhanced radiosensitivity by inducing G2/M arrest, while Sp1 overexpression reduced it, linked to CDK1 upregulation.

Conclusions:

  • Sp1 contributes to cervical cancer radioresistance by inhibiting G2/M phase arrest through targeting CDK1.
  • Sp1 represents a potential therapeutic target to improve radiotherapy outcomes in cervical cancer.
  • Targeting Sp1 may offer a strategy to overcome radioresistance and enhance treatment efficacy.
Keywords:
CDK1G2/M phaseSp1cervical cancerradioresistance

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