Polymorphisms of microRNA-Binding Sites in Integrin Genes Are Associated with Oral Squamous Cell Carcinoma Susceptibility and Progression

Polymorphisms of microRNA-Binding Sites in Integrin Genes Are Associated with Oral Squamous Cell Carcinoma Susceptibility and Progression
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整合素基因中 microRNA 结合位点的多态性与口腔鳞状细胞癌的易感性和进展相关

DOI:
10.1620/tjem.233.33
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发表时间:
2014-05-01
影响因子:
2.2
通讯作者:
Chen, Qianming
Chen, Qianming
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Yun;Long, Long;Chen, Qianming

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整合素是重要的细胞表面受体,在细胞与细胞外环境的连接中起重要作用。整合素已得到证实。在口腔鳞状细胞癌(OSCC)的发展过程中起着重要作用。本研究旨在探讨整合素基因microRNA结合位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)与中国汉族人群口腔鳞癌易感性及进展的关系。我们从三个独立的医疗中心招募了167名OSCC患者和200名无癌症对照。成功完成了5个选定的整合素SNP的基因分型:rs 1062484(整合素α 3)、rs 11902171(整合素α v)、rs 17468(整合素β 1)、rs3809865(整合素β 3)和rs 2675(整合素β 5)。结果表明,整合素β 3基因3 '非翻译区rs3809865 T/A(T → A)的A等位基因多态性与口腔鳞癌的发病风险相关(p < 0.05)。此外,该SNP与患者外周血单个核细胞中整合素β 3 mRNA表达水平之间的关联分析表明,携带A等位基因的OSCC患者具有较低的整合素β 3表达水平(p = 0.047)。同时生存分析显示整合素β 5基因3 ' UTR的另一个多态性位点rs 2675 A/C(核苷酸由A变为C)的C等位基因与口腔鳞癌的发生发展有关。总体而言,我们的研究结果表明,rs3809865和rs 2675可能有助于中国汉族人群口腔鳞癌的风险和进展。这两个SNPs有可能成为口腔鳞癌诊断和预后的潜在生物标志物。
Integrins, which act as an important role in the connection between cells and extra-cellular environments, are important cell surface receptors. Integrins have been demonstrated. to play critical roles in many aspects of the progression of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in microRNA-binding sites of integrin genes and the susceptibility and progression of OSCC in Chinese Han Population. We recruited 167 OSCC patients and 200 cancer-free controls from three independent medical centers. Genotyping was completed successfully for the five selected integrin SNPs: rs1062484 (integrin alpha 3), rs11902171 (integrin alpha v), rs17468 (integrin beta 1), rs3809865 (integrin beta 3), and rs2675 (integrin beta 5). The results demonstrated that the A allele of rs3809865 T/A (a T-to-A nucleotide change), a functional polymorphism in the 3 ' UTR of integrin beta 3 gene, was associated with OSCC risk (p < 0.05). In addition, the association analysis between this SNP and integrin beta 3 mRNA expression level in the patients' peripheral blood mononuclear cells indicated that OSCC patients carrying the A allele would have a lower integrin beta 3 expression level (p = 0.047). Meanwhile, survival analysis showed that the C allele of rs2675 A/C (nucleotide change from A to C), another 3 ' UTR polymorphism in integrin beta 5 gene, was related with progression of OSCC. Overall, our results suggest that rs3809865 and rs2675 may contribute to OSCC risk and progression in Chinese Han Population. These two SNPs may be used as potential diagnostic and prognostic biomarkers for OSCC in future.