Abstract
BACKGROUND: miRNAs play a crucial role in the genesis of cancer, either as tumor suppressor genes or as oncogenes. Single Nucleotide Polymorphisms (SNPs) in the seed region of microRNAs (miRNAs) can dysregulate their levels in the tissues and thereby affect carcinogenesis. The association of SNP in miR-146a (rs2910164) with the risk of oral squamous cell carcinoma (OSCC) has not been understood. OBJECTIVE: In the present study, we have determined the association and functional significance of miR-146a (rs2910164) SNP with susceptibility to OSCC predisposition. METHODS: In the present case-control study, we enrolled 430 subjects from central India (215 OSCC cases and 215 healthy controls). We performed genotyping by Kompetitive Allele Specific PCR (KASP), and their correlation with OSCC susceptibility was analyzed. miRNA expression profiling in tumor tissues and adjacent normal tissues from six OSCC patients was done by a NanoString n-Counter-based assay. Subsequently, gene ontology and pathway analysis were performed with FunRich version 3.13. RESULTS: The CC genotype of rs2910164 miR-146a was significantly associated with the increased risk for OSCC (CC vs GC, OR = 2.62; 95% CI: 1.48-4.66; p value = 0.001). However, the GC genotype was protective with GC vs CC (OR = 0.38, 95%CI =0.21-0.67, p-value = 0.001), and GC vs GG (OR = 0.58, 95%CI = 0.37-0.89, p-value = 0.01). CONCLUSION: Our finding suggests that SNP rs2910164 of miR-146a may be a genetic risk factor for OSCC susceptibility in the Central India population. However, more extensive multicenter studies are required to validate these findings.