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image of PPA1, TRIM68 and FBXO46: Potential Therapeutic Targets for Triple Negative Breast Cancer

Abstract

Background

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.

Method

The cell cytotoxicity of ML364 (2-(4-Methylphenylsulfonamido)-N-(4-phenylthiazol-2-yl)-4-(trifluoromethyl)benzamide) was measured at different concentrations of ML364 in TNBC-treated and untreated cells. The 2DE and LC-MS/MS analysis were used for protein identification of differentially expressed proteins. Furthermore, the quantitation of gene expression was demonstrated using RT-qPCR. TIMER, HPA, and UALCAN databases were utilized for further analysis.

Results

Differentially expressed proteins and genes after ML364 treatment in TNBC were found to be linked with the USP2 (ubiquitin specific peptidase 2)-mediated pathway. Our results demonstrate that differentially identified proteins, including PPA1, TRIM68, and FBXO46, could be a potential prognostic biomarker for TNBC. Further analysis through the UALCAN and HPA databasess shows the high expression of these proteins in primary breast tumors, which is in contrast to normal. The induction of ML364 significantly reduced the expression of PPA1, TRIM68, and FBXO46 proteins and induced cell cytotoxicity in TNBC cells.

Conclusion

This study provides an understanding of the USP2-mediated signaling pathway in TNBC, emphasizing the role of USP2 and its substrates with apoptotic genes. Our results offer insight into the USP2-mediated cellular mechanism after ML364 treatment in TNBC that could be a potential therapeutic candidate.

© 2025 Bentham Science Publishers
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2025-01-01
2025-01-22

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PPA1, TRIM68 and FBXO46: Potential Therapeutic Targets for Triple Negative Breast Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0113892037334325241014053319
/content/journals/cpps/10.2174/0113892037334325241014053319
/content/journals/cpps/10.2174/0113892037334325241014053319
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  • Article Type:     Research Article
Keywords: TRIM68 (tripartite motif containing 68) ; USP2 (ubiquitin specific peptidase 2) ; FBXO46 (F-Box Protein 46) ; ML364(2-(4-Methylphenylsulfonamido)-N-(4-phenylthiazol-2-yl)-4-(trifluoromethyl)benzamide) ; UPS (ubiquitin-proteasome system) ; PPA1 (Inorganic pyrophosphatase 1) ; TNBC (Triple-negative breast cancer) ; and DUBs (Deubiquitinating proteases)

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