Abstract
MicroRNAs (miRNAs) have been reported to play a key role in oncogenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the miRNA-mRNA interactions, hence promoting tumorigenesis. In the present study, we hypothesized that potentially functional polymorphisms in miRNA processing genes may contribute to head and neck cancer (HNC) susceptibility. To test this hypothesis, we genotyped three SNPs at miRNA binding sites of miRNA processing genes (rs1057035 in 3′UTR of DICER, rs3803012 in 3′UTR of RAN and rs10773771 in 3′UTR of HIWI) with a case-control study including 397 HNC cases and 900 controls matched by age and sex in Chinese. Although none of three SNPs was significantly associated with overall risk of HNC, rs1057035 in 3′UTR of DICER was associated with a significantly decreased risk of oral cancer (TC/CC vs. TT: adjusted OR = 0.65, 95% CI = 0.46–0.92). Furthermore, luciferase activity assay showed that rs1057035 variant C allele led to significantly lower expression levels as compared to the T allele, which may be due to the relatively high inhibition of hsa-miR-574-3p on DICER mRNA. These findings indicated that rs1057035 located at 3′UTR of DICER may contribute to the risk of oral cancer by affecting the binding of miRNAs to DICER. Large-scale and well-designed studies are warranted to validate our findings.
Highlights
Head and neck cancer (HNC), especially squamous cell carcinoma of the head and neck (SCCHN), is the sixth most common malignancy worldwide, accounting for an estimated 650 000 new cancer cases and 350 000 cancer deaths every year [1,2]
In this case-control study of 397 HNC patients and 900 cancerfree controls in a Chinese population, we investigated the associations between three SNPs in 39UTR of miRNA biosynthesis genes and risk of HNC
We did not find evidence for a main effect of each SNP on overall HNC risk, the subgroup analysis of HNC showed that variant genotypes of rs1057035 were associated with the risk of HNC arising at oral cavity
Summary
Head and neck cancer (HNC), especially squamous cell carcinoma of the head and neck (SCCHN), is the sixth most common malignancy worldwide, accounting for an estimated 650 000 new cancer cases and 350 000 cancer deaths every year [1,2]. Studies reported that genetic factors including family history and genetic variants in multiple biological pathways were involved in the development of HNC [3]. Studies have showed that miRNAs are involved in a variety of biologic processes, including cell cycle regulation, differentiation, development, metabolism and aging. The biogenesis of miRNAs is a complex process involving multiple proteins and RNAs [8]. The pre-miRNA is translocated to the cytoplasm through the assistance of Ran-GTPase and Exportin-5 (XPO5), where it is further processed by a protein complex including DICER, leading to the production of double-stranded miRNA duplex.[10]. Growing evidence shows that key components in the biosynthetic pathway of miRNA play important roles in the development or prognosis of human cancers including HNC [11,12,13]
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