The association between miR‐499a polymorphism and oral squamous cell carcinoma progression

Abstract

To investigate the association of miR-499a genetic polymorphism with the risk of oral leukoplakia, oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC), and clinicopathological outcomes of OSCC. The genotyping of miR-499a T>C (rs3746444) using TagMan assay was conducted in two case-control studies of 1549 subjects. miR-499a-5p and miR-499a-3p were assayed using stem-loop RT-PCR for 63 paired OSCC and adjacent normal tissues. T/C+C/C genotypes [adjusted odds ratio (AOR) 1.84, P=0.032] and C allelic type (AOR 1.91, P=0.007) at miR-499a T>C were associated with an increased risk of BQ-related OSF as compared to those with T/T genotype or T allelic type, respectively. Conversely, T/C+C/C genotypes and C allelic type decreased the risk of OSCC, especially for non-BQ-related OSCC (for genotype: AOR 0.49, P=0.010; for allelic type: AOR 0.50, P=0.007). Additionally, downregulation of miR-499a-5p was found in OSCC tissues (P=0.001) and correlated with the TT genotype (P=0.001). The T/C+C/C genotypes of MiR-499a may contribute to an increased risk of BQ-related OSF, but a decreased risk of OSCC. miR-499a T>C influences the expression levels of miR-499a-5p during the tumorigenesis of OSCC.