Aierken Kailibinuer, Dong Zhihong, Abulimiti Tangnuer, Zhang Yuanyuan, Abuduxikuer Guzhalinuer, Tuerxun Gulixian, Abudurexiti Guligeina, Maimaitiaishan Aziguli, Mijiti Patiman, Abulizi Guzhalinuer
5th Department of Gynecology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Outpatient Department, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Mol Genet Genomic Med. 2019 May;7(5):e626. doi: 10.1002/mgg3.626. Epub 2019 Mar 4.
Cyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females.
The genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real-time PCR.
CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37-0.99, p = 0.043) and log-additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38-1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high-grade cervical cancer in different genetic models as well (p < 0.05). Dataset-based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors.
Our results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.
细胞周期蛋白依赖性激酶6（CDK6）在恶性肿瘤中起关键作用，而在宫颈癌发生发展方面的报道较少。本研究旨在评估CDK6 3'非翻译区（3'UTR）多态性对维吾尔族女性宫颈癌易感性的影响。
采用Agena MassARRAY平台，在306例宫颈癌病例和310例健康对照中鉴定6个CDK6变异体（rs8179、rs42032、rs42033、rs42034、rs42035和rs42038）的基因型。使用条件逻辑回归分析在遗传模型下评估候选单核苷酸多态性（SNP）与宫颈癌风险的关联。利用在线数据库对SNP功能进行预测的生物信息学分析。还通过实时PCR检测肿瘤组织与正常宫颈样本之间的表达差异。
在等位基因模型（rs8179和rs42033：OR = 0.60，95%CI：0.37 - 0.99，p = 0.043）和对数加性模型（rs8179和rs42033：OR = 0.62，95%CI：0.38 - 1.00，p = 0.047）下，CDK6 rs8179和rs42033与维吾尔族宫颈癌风险降低相关。Rs8179、rs42032和rs42033在不同遗传模型中也与高级别宫颈癌易感性相关（p < 0.05）。基于数据集的分析也揭示了这些显著SNP的潜在影响。此外，在宫颈肿瘤中检测到CDK6的异常表达。
我们的结果提示了CDK6 3'UTR多态性与宫颈癌发病机制之间的关系，以及CDK6在维吾尔族女性宫颈癌发生发展中的作用。
