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

Hailing Pan,1,* Zixin Huang,2,* Aiping Li,1 Meiya Li,3 Yanxing Li,1 Ya Lin,1 Jiayin Cai1 1Department of Oncology, Traditional Chinese Medical Hospital of Wenling Affiliated to Zhejiang Chinese Medical University, Zhejiang, 317500, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, 310053, People’s Republic of China; 3Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Zhejiang, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiayin Cai, Department of Oncology, Traditional Chinese Medical Hospital of Wenling affiliated to Zhejiang Chinese Medical University, No. 190, Taiping South Road, Taiping Street, Zhejiang, 317500, People’s Republic of China, Email jiayincai2025190@163.comBackground: 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. The image consists of three main sections. It starts with ’rs8067576’ leading to ’Pre-miRNA’, which is processed by ’Dicer’ into a ’miRNA/miRNA duplex’ and finally into ’miRNA’. The middle section displays two graphs labeled ’Poor prognosis’. The first graph shows survival probability over ’PFS Months’ with a p-value of 0.0015, comparing ’rs8067576 TT/TA’ and ’AA’. The second graph shows survival probability over ’OS Months’ with a p-value of 0.00066, also comparing ’rs8067576 TT/TA’ and ’AA’. Both graphs include ’Number at risk’ data. The right section illustrates cancer progression with images labeled ’Proliferation of cancer cells’, ’Cancer cell (epithelial)’, ’Migratory cancer cell (mesenchymal)’ and ’Local invasion’. The text ’Increased cell proliferation, migration and invasion’ is shown above these illustrations.Diagram of miRNA processing, prognosis graphs and cancer cell progression.Keywords: miR-423-5p, single nucleotide polymorphism, triple-negative breast cancer, genetic susceptibility, cellular function