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

YUN WANG,¹ LONG LONG,¹ TAIWEN LI,¹ YU ZHOU,¹ LU JIANG,¹ XIN ZENG,¹ HONGXIA DAN,¹ GA LIAO,¹ GANG LUO,² HUI WANG,³ MIN ZHOU,¹ YI XU,^1,4 JING LI¹ and QIANMING CHEN¹

¹State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
²Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
³Department of Oral Medicine, School of Stomatology, Capital Medical University, Beijing, P.R. China
4 Department of Periodontology, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China

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 α3), rs11902171 (integrin αv), rs17468 (integrin β1), rs3809865 (integrin β3), and rs2675 (integrin β5). 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 β3 gene, was associated with OSCC risk (p < 0.05). In addition, the association analysis between this SNP and integrin β3 mRNA expression level in the patients’ peripheral blood mononuclear cells indicated that OSCC patients carrying the A allele would have a lower integrin β3 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 β5 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.

keywords —— integrin; microRNA; multicenter case-control study; oral squamous cell carcinoma; single nucleotide polymorphism

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Tohoku J. Exp. Med., 2014, 233, 33-41

Correspondence: Jing Li, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin Nan Road, Chengdu 610041, P.R. China.

e-mail: lijing1984@scu.edu.cn