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 the SGK3 gene and the risk of nasopharyngeal carcinoma (NPC). Methods: Three SGK3 loci, 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 of SGK3 messenger 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: SGK3 rs77572541 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). The SGK3 rs11994200 locus C allele was a major risk factor for NPC (odds ratio = 2.68, 95% CI = 1.63-4.39, p < 0.01). Similarly, carriers of the C allele of the SGK3 rs78158330 locus 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. The SGK3 rs77572541 locus G allele is the target of hsa-miR-379-5p and hsa-miR-3529-5p, but the A allele is not. The SGK3 rs11994200 locus C allele was the target of hsa-miR-4320, and the G allele was the target of hsa-miR-498. The SGK3 rs78158330 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 the SGK3 loci rs77572541, rs11994200, and rs78158330 are significantly associated with the risk for NPC. These effects may be related to the influence of miRNAs on different alleles, but this needs to be verified both in vitro and in vivo.