Genetic variants of miRNA sequences and non-small cell lung cancer survival

来源 :南京医科大学学报(自然科学版) | 被引量 : 0次 | 上传用户:pzl_530
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Recent evidence indieates that small noneoding RNA molecules known as microRNAs(miRNAs)van function as tumor suppressors and oncogenes.Mutation,misexpression,and altered mature miRNA prueessing are implicated in carcinogenesis and tu- mor progression.Because SNPs in pre-miRNAs could alter miRNA processing,expression,and/or binding to target mRNA,we con- ducted a systematic survey of common pre-miRNA SNPs and their surrounding regions and evaluated in detail the association of 4 of these SNPs with the survival of individuals with non-small cell lung cancer(NSCLC).When we assumed that disease susceptibility was inherited as a recessive phenotype,we found that the rs11614913 SNP in hsa-mir-196a2 was associated with survival in individ- uals with NSCLC.Specifically,survival was significantly decreased in individuals who were homozygous CC at SNP rs11614913.In the genotype-phenoiype correlation analysis of 23 human lung cancer tissue samples,rs11614913 CC was associated with a statisti- cally signifieant increase in mature hsa-mir-196a expression hut not with changes in levels of the precursor,suggesting enhanced processing of the pre-miRNA to its mature form.Furthermore,binding assays revealed that the rs11614913 SNP can affect hinding of mature hsa-mir-196a2-3p to its target mRNA.Therefore,the rs11614913 SNP in hsa-mir-196a2 may be a prognostic biomarker for NSCLC.Further characterization of miRNA SNPs may open new avenues for the study of cancer and therapeutic,interventions.
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