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Genetic Correlation of miR-423 Polymorphism rs8067576 with Progression and Prognosis of Triple-Negative Breast Cancer
Hailing Pan1, Zixin Huang2, Aiping Li1
1Department of Oncology, Traditional Chinese Medical Hospital of Wenling Affiliated to Zhejiang Chinese Medical University, Zhejiang, 317500, People's Republic of China.
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.
Insights
The miR-423 rs8067576 SNP increases triple-negative breast cancer risk and severity. This genetic variant enhances tumor cell proliferation and invasiveness, leading to poorer survival outcomes in TNBC patients.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Single nucleotide polymorphisms (SNPs) in microRNAs can alter their function and influence disease susceptibility.
- MicroRNA-423 (miR-423) genetic variations are implicated in various cellular processes and disease states.
Purpose of the Study:
- To investigate the association between the miR-423 rs806757 SNP and the risk, severity, and survival of triple-negative breast cancer (TNBC).
- To elucidate the molecular mechanisms by which the miR-423 rs806757 SNP affects TNBC progression.
Main Methods:
- Genotyping of 300 TNBC patients and 300 controls for the miR-423 rs806757 SNP.
- Analysis of SNP association with relapse-free survival (RFS) and 5-year survival.
- In vitro assays (CCK-8, Transwell) to assess the variant's impact on tumor cell proliferation, migration, and invasion.
- In silico target prediction and pathway enrichment analysis (GO/KEGG).
Main Results:
- The rs8067576 polymorphism showed a significant difference in genotype distribution between TNBC patients and controls.
- Carriers of the AA genotype had larger tumors, lymph node involvement, and advanced stage (III-IV), along with reduced RFS and 5-year survival.
- The A allele of rs8067576 significantly increased miR-423-5p expression, promoting tumor cell proliferation, motility, and invasiveness.
- Wnt and Ras signaling pathways were identified as key downstream effectors regulated by miR-423-5p.
Conclusions:
- The miR-423 rs8067576 SNP is a susceptibility locus for TNBC, associated with increased risk, earlier relapse, and shorter survival.
- The rs8067576 polymorphism enhances miR-423-5p expression, thereby promoting tumor cell aggressiveness and contributing to TNBC progression.
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