The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology

Li Xia1, Minjie Wang2, Hongying Li3

  • 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Cancer Medicine
|May 26, 2018
PubMed

Insights

Rad21 gene expression is elevated in cervical cancer (CC), correlating with increased risk and poor survival. Targeting Rad21 may offer new therapeutic strategies for CC by impacting cell cycle and tumor suppressor gene export.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Advanced, recurrent, and refractory cervical cancer (CC) presents a significant therapeutic challenge, necessitating novel molecularly targeted drugs.
  • Rad21 is a key regulatory gene involved in sister chromatid dissociation during mitosis.

Purpose of the Study:

  • To investigate the role and impact of Rad21 expression in the development and progression of cervical cancer.
  • To explore the potential of Rad21 as a therapeutic target for CC.

Main Methods:

  • Analysis of Rad21 expression in CC and cervical intraepithelial neoplasia III tissues.
  • Genotyping of specific Rad21-related SNPs (rs4570, rs4579555) and haplotype analysis.
  • Functional studies using Rad21-specific shRNA to assess effects on cancer cell proliferation, migration, invasion, cell cycle, and radiosensitivity.
  • Analysis of Rad21's influence on downstream gene expression (XPO1, CyclinB1, CDK1, P21, P27, P53).
  • Utilizing TCGA database for correlation analysis between Rad21 expression, patient survival, and XPO1 expression.
  • KEGG pathway analysis to determine Rad21's involvement in cellular processes.

Main Results:

  • Rad21 expression was significantly increased in CC and cervical intraepithelial neoplasia III.
  • Specific genotypes (rs2289937 C) and haplotypes (haplotype 1, low frequency of haplotype 6) were associated with CC risk.
  • Rad21 knockdown reduced cancer cell proliferation, migration, and invasion, induced G2/M phase arrest, and enhanced radiosensitivity.
  • Rad21 influenced the expression of cell cycle regulators and XPO1.
  • TCGA data indicated Rad21 expression correlates with poor CC survival and increased XPO1 expression.
  • KEGG pathway analysis revealed Rad21's broad involvement in the cell cycle and RNA transport via XPO1.

Conclusions:

  • Rad21 overexpression is implicated in cervical cancer development and progression.
  • Rad21 plays a role in regulating the cell cycle and nuclear export of tumor suppressor genes via XPO1.
  • Targeting Rad21 presents a potential therapeutic strategy for cervical cancer.

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