Risk of Nasopharyngeal Carcinoma Associated with Single Nucleotide Polymorphisms in the MicroRNA Binding Site of SGK3

Objective:Serum/glucocorticoid regulated kinase is a serine/threonine kinase that is involved in regulating cell proliferation, apoptosis, the cell cycle, and ion channel function. The aim of this study was to analyze the relationship between single nucleotide polymorphisms (SNPs) in the microRNA (miRNA) binding site of theSGK3gene and the risk of nasopharyngeal carcinoma (NPC). Methods:ThreeSGK3loci, rs77572541, rs11994200, and rs78158330, were genotyped in 226 NPC patients and 226 healthy controls via Sanger sequencing. Quantitative real-time polymerase chain reaction was used to analyze levels ofSGK3messenger RNA (mRNA), hsa-miR-3529-5p, hsa-miR-379-5p, hsa-miR-498, hsa-miR-4320, and hsa-miR-590-3p. Western blot analysis was used to assess serum and glucocorticoid regulated kinase 3 (SGK3) protein expression. Results:SGK3rs77572541 locus G allele carriers were 3.47 times more likely to develop NPC than carriers of the A allele (95% confidence interval [CI] = 1.98-6.09,p < 0.01). TheSGK3rs11994200 locus C allele was a high risk factor for NPC (odds ratio = 2.68, 95% CI = 1.63-4.39,p < 0.01). Similarly, carriers of the C allele ofSGK3rs78158330 were 3.36 times more likely to develop NPC than those with the T allele (95% CI = 1.96-5.73,p < 0.01). The SGK3 protein was highly expressed in NPC. TheSGK3rs77572541 locus G allele is the target of hsa-miR-379-5p and hsa-miR-3529-5p, but the A allele is not. TheSGK3rs11994200 locus C allele was the target of hsa-miR-4320, and the G allele was the target of hsa-miR-498.SGK3rs78158330 locus T allele was the target of hsa-miR-590-3p. Hsa-miR-3529-5p, hsa-miR-379-5p, and hsa-miR-4320 were down-regulated in NPC tissues (p < 0.01), whereas hsa-miR-498 and hsa-miR-590-3p were highly expressed (p < 0.01). Conclusions:SNPs at theSGK3loci rs77572541, rs11994200, and rs78158330 are significantly associated with risk for NPC. These effects may be related to the influence of miRNAs on different alleles, but this needs to be verified bothin vitroandin vivo.