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

Abstract

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 α v), rs17468 (integrin β 1), rs3809865 (integrin β 3), and rs2675 (integrin β 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 β3 gene, was associated with OSCC risk (p < 0.05). In addition, the association analysis between this SNP and integrin β 3 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.

A Functional Variant at miR-520a Binding Site in PIK3CA Alters Susceptibility to Colorectal Cancer in a Chinese Han Population

“…miRNAs bind to the 3′-untranslated region (3′-UTR) of mRNA through the seed region and activate the degradation of mRNA, thus repressing translation [ 10 , 11 ]. As the binding between mRNA and miRNA is based on complementary base pairing, a single nucleotide polymorphism (SNP) in the 3 ′- UTR or seed region would affect the binding efficiency, which may lead to change of the expression level of their target genes [ 12 ]. For example, the miR-184 binding site SNP (rs8126 T>C) in the 3′-UTR of TNFAIP2 could modulate TNFAIP2 expression and contributes to neck squamous cell carcinoma (HNSCC) susceptibility [ 13 ].…”

Non-coding RNA regulation of integrins and their potential as therapeutic targets in cancer

“…Three beta group integrins have such sequence changes. The ITGB3 rs3809865 T/A variant was significantly associated with oral squamous cell carcinoma risk and reduced integrin expression, the SNP being in a putative MRE for miRNAs miR-26b, miR-330, and miR-324-5p [ 77 ]. ITGB4 rs743554 G/A allele, at a miR-34a MRE, was associated with BC progression, reduced survival, and metastasis [ 78 ].…”

microRNAs deregulation in head and neck squamous cell carcinoma

“…The variant alleles of SNVs integrin subunit beta 3 ( ITGB3 ) rs3809865 A 68 and integrin subunit beta 5 ( ITGB5 ) rs2675 C, 68 and the wild‐type allele of high mobility group box 1 ( HMGB1 ) rs1045411 C 69 were associated with lower mRNA expression compared to the respective T and A wild‐type alleles, and with the T variant allele, due to miR‐26b, miR‐330, and miR‐324‐5p; miR‐215 and miR‐440; and miR‐505‐5p binding, respectively, decreasing cell adhesion and increasing cell proliferation and migration, and thus favoring OSCC risk and progression. Likewise, the wild‐type A allele of SNV protein lin‐28 homolog B ( LIN28B ) rs221636 70 was associated with higher mRNA expression compared to the T variant allele, due to disruption of miR‐548p binding, negatively regulating tumor suppressor miRNAs processing, and thus increasing OSCC risk.…”