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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
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.
Abstract:
The therapeutic challenge of advanced, recurrent, and refractory cervical cancer (CC) needs to develop new molecularly targeted drugs. Rad21 is an important regulatory gene that maintains the correct dissociation of sister chromatids during cell mitosis. The aim of this study was to investigate the effect of Rad21 on CC. Rad21 expression in CC and cervical intraepithelial neoplasia III was significantly increased. Women with the rs2289937 C genotype (CC+CT) of rs4570 and rs4579555 genotypes and haplotype 1 (TTTCAGGCGC) were significantly associated with CC risk, while women with low frequencies of haplotype 6 (TTTTAGGCGC) also increased the risk of CC.Rad21-specific shRNA decreased cancerous cell proliferation, migration, and invasion and increased the proportion of cells in G2/M phase as well as sensitivity to radiation. The Rad21 influenced the expression of XPO1, CyclinB1, CDK1, P21, P27, and P53 through up-and downregulating the Rad21 expression. The TCGA database of CC also showed that Rad21 expression was associated with poor disease survival and XPO1 expression. Moreover, the KEGG pathway indicated that Rad21 is broadly involved in the cell cycle and RNA transportation via XPO1. This suggests that Rad21 involves the development of cervical cancer possibly by participating in the regulation of cell cycle and the nuclear output of the tumor suppressor gene via XPO1.
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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