Genetic Correlation of miR-423 Polymorphism rs8067576 with Progression and Prognosis of Triple-Negative Breast Cancer.

Abstract

Background: Single nucleotide polymorphisms (SNPs) of microRNAs can affect the functional activity of microRNA, thereby relating to disease susceptibility.

Objective: The study systematically examined the impact of miR-423 rs806757 SNP on triple-negative breast cancer (TNBC) risk and severity and dissected the attendant molecular mechanism.

Materials and methods: Three hundred TNBC patients and 300 controls were genotyped for miR-423 rs806757, and its association with relapse-free survival (RFS) and 5-year survival was analyzed. CCK-8/Transwell assays quantified the variant's influence on tumor cell proliferation, migration and invasion. In-silico target prediction followed by GO/KEGG profiling mapped the downstream pathways.

Results: A significant difference was detected in the genotype distribution of rs8067576 polymorphism between TNBC and controls. And cases harboring rs8067576 AA allele exhibited a higher prevalence of tumors >5 cm, lymph-node involvement, and higher stage (III-IV). AA genotype carriers displayed markedly reduced RFS and 5-year overall survival, and held a conspicuous rise in miR-423-5p levels compared with patients bearing alternative genotypes. Cell-based assays revealed that introducing rs8067576-A allele into tumor cells robustly boosted tumor-cell proliferation, motility, and invasiveness relative to T allele. Subsequent target prediction and pathway enrichment identified Wnt and Ras signaling as the principal downstream effector modules of miR-423-5p.

Conclusion: MiR-423 rs8067576 was a susceptibility locus for TNBC and linked to earlier relapse and shorter 5-year survival. Rs8067576 boosted miR-423-5p expression, thereby enhancing tumor-cell proliferation, motility, and invasiveness.