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Variations in the Wnt/?-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility.

ABSTRACT: Background:Cervical cancer is the fourth most common and fatal tumor among women worldwide. The Wnt/?-catenin signaling pathway was etiologically involved in the cervical cancer model. Herein, we aimed to investigate whether germline genetic variations within the Wnt/?-catenin pathway can be genetic risk factors of cervical cancer. Patients and Methods:A total of 305 samples (147 patients, 158 controls) were included. Eight genetic variations located in APC (rs454886), GSK3? (rs3755557), CTNNB1 (rs11564475, rs1798802, rs3864004, rs2293303, and rs4135385), and TCF7L2 (rs7903146) were genotyped via Sanger sequencing. The ? 2 test and non-conditional logistic regression were used in the single-locus analysis. Gene-gene interactions and haplotype construction in case-control samples were performed by the GMDR method and Haploview software, respectively. Results:The frequency of CTNNB1 rs1798802 GA+AA genotype was significantly lower in cervical cancer patients adjusted for age (OR=0.626, 95% CI=0.398-0.984). The mutant alleles of rs3864004 (A) and rs2293303 (T) located in CTNNB1 showed 1.513 (1.038-2.207), and 1.654 (1.020-2.683) fold increased risk of cervical cancer, respectively. Haplotype analysis showed no association between haplotypes of the CTNNB1 gene and cervical cancer risk. No significant contribution of interactions among genes in the Wnt pathway was identified. Conclusion:We concluded that the genetic variants in the CTNNB1 gene might contribute to the development of cervical cancer.

SUBMITTER: Wang B

PROVIDER: S-EPMC7247596 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Variations in the Wnt/β-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility.

Wang Bingqi B Wang Min M Li Xianping X Yang Min M Liu Lei L

Pharmacogenomics and personalized medicine 20200520

<h4>Background</h4>Cervical cancer is the fourth most common and fatal tumor among women worldwide. The Wnt/β-catenin signaling pathway was etiologically involved in the cervical cancer model. Herein, we aimed to investigate whether germline genetic variations within the Wnt/β-catenin pathway can be genetic risk factors of cervical cancer.<h4>Patients and methods</h4>A total of 305 samples (147 patients, 158 controls) were included. Eight genetic variations located in APC (rs454886), GSK3β (rs37 ...[more]

PMID: 32547159

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Project description:BACKGROUND:Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression. MATERIALS:Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/?-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation. RESULTS:We discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/?-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo. CONCLUSION:Our study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/?-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.

Dataset Information

Variations in the Wnt/?-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility.

Publications

Variations in the Wnt/β-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility.

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