# Low Expression of UBE2Z, a Target Protein of miR-500a, Is Associated with Poor Prognosis in Triple-Negative Breast Cancer

## TL;DR

Low levels of UBE2Z, a protein targeted by miR-500a, are linked to worse outcomes in triple-negative breast cancer patients.

## Contribution

Identified UBE2Z as a novel prognostic biomarker in triple-negative breast cancer through miRNA and bioinformatics analysis.

## Key findings

- miR-500a and UBE2Z expression levels are associated with prognosis in TNBC.
- UBE2Z is a target of miR-500a and its low expression correlates with poor survival.
- Differentially expressed miRNAs are linked to cell cycle pathways in TNBC.

## Abstract

Triple-negative breast cancer (TNBC) exhibits diverse histological and molecular characteristics. TNBC patients also have the poorest prognoses among those with various breast cancer subtypes, and no effective treatment strategy has been established for TNBC beyond non-specific chemotherapy. Recent studies have reported that the dysregulation of miRNAs is associated with tumor behavior, prognosis, and treatment responses in TNBC patients. Therefore, this study was conducted to identify miRNAs and key target proteins potentially associated with TNBC prognosis. Fresh-frozen tissue from relapsing and non-relapsing TNBC cases was examined for differentially expressed miRNAs using the Affymetrix GeneChip miRNA 4.0 array, while target genes and proteins were predicted using the miRwalk 2.0 database. The clinical significance of each differentially expressed miRNA was evaluated using the BreastMark database. Additional bioinformatics analyses were conducted to reveal associations with tumor-related signaling pathways; these analyses included protein–protein interaction network construction and Kyoto Encyclopedia of Genes and Genomes pathway annotation. Gene chip analysis identified three upregulated miRNAs (miR-500a, miR-501-3p, and miR-502-3p) and two downregulated miRNAs (miR-6798-5p and miR-7150) in patients with recurrence, and further bioinformatics analyses revealed that target proteins were significantly associated with cell cycle pathways. In addition, low expression of the miR-500a target protein UBE2Z was significantly associated with a poor prognosis. The expression levels of miR-500a and UBE2Z might be useful prognostic biomarkers in TNBC.