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.

Abstract

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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