韩国人群中与肾癌相关的miRNA相关SNP的鉴定

Background : MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally and play critical roles in tumor development. Genetic variants located within miRNA precursor, mature, or seed regions may influence miRNA maturation or target binding, thereby affecting cancer susceptibility. This study aimed to identify miRNA-related single nucleotide polymorphisms (SNPs) associated with kidney cancer in a Korean population. Methods : We performed genome-wide association analyses of kidney cancer in the Korean population using datasets from the Korean Cancer Prevention Study-II (KCPS-II) and the Korean Genome and Epidemiology Study (KOGES). A subsequent meta-analysis identified three miRNA-related single nucleotide polymorphisms (SNPs) significantly associated with kidney cancer. miRNA-related variants were annotated based on their location within pre-miRNA, mature miRNA sequences, or seed regions using the miRNASNP-v4 database. Functional relevance was interpreted according to predicted effects on miRNA biogenesis and target-binding specificity. Results: miRNA-related SNPs showed genome-wide significant associations with kidney cancer. The pre-miRNA variant rs1414273 , located in the hairpin of hsa-mir-548ac, demonstrated a strong association (effect = -1.1112, SE = 0.0498, P = 3.46×10⁻¹¹⁰). This variant may alter Drosha processing efficiency, thereby affecting the production of miR-548ac. Because miR-548ac regulates genes involved in inflammatory signaling and protein quality-control pathways, disruption of its maturation may influence cellular stress responses relevant to renal tumorigenesis. The mature miRNA variant rs73239138 , positioned within hsa-miR-1269a, showed a similarly robust association (effect = 1.076, SE = 0.0491, P = 1.71×10⁻¹⁰⁶). miR-1269a is an oncogenic miRNA overexpressed in at least nine cancers and regulates key targets (CXCL9, SOX6, FOXO1, ATRX, RASSF9, SMAD7, HOXD10, VASH1) through pathways such as TGF-beta, PI3K/AKT, p53, and caspase-9 signaling; thus, a sequence alteration within its mature strand may affect RISC loading, target recognition, and amplify oncogenic post-transcriptional regulation in kidney cancer. The seed-region variant rs2925980 in hsa-miR-7854-3p also reached genome-wide significance (effect = -1.0276, SE = 0.0494, P = 5.1×10⁻⁹⁶). Seed mutations can reprogram target specificity by creating or disrupting binding sites, suggesting that altered miR-7854-3p targeting contributes to renal cancer susceptibility. Conclusions: These findings indicate that pre-miRNA, mature miRNA, and seed-region variants contribute to kidney cancer susceptibility in the Korean population. The identified SNPs provide a basis for functional validation and the development of miRNA-based biomarkers in kidney cancer.