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Cancer BiologybioRxiv

Tristetraproline in breast cancer: treat or trick?

S. Kropyvko, A. Hubiernatorova, O. Mankovska, L. Syvak, N. Verovkina, S. Lyalkin, K. Lavrynenko, I. Ivasechko, R. Stoika, A. Rynditch

Abstract

Breast cancer is one of the most common types of cancer. It is very heterogeneous, hence still complicated to diagnose despite of decades of research. Post-transcriptional regulation of gene expression is crucial for modulation of cell networking and is performed via different regulatory molecules. Tristetraproline (TTP) is RNA-binding protein which binds to AU-rich elements within its target mRNAs and negatively regulates multiple transcripts, including pro-inflammatory and pro-oncogenic. Its expression level correlates with patient outcomes in different types of cancer and is considered as a potential molecular marker. Here we examined TTPs expression level in different molecular subtypes of breast cancer. Our findings show that TTP expression is significantly higher in HER2-enriched breast cancer compared to other types and adjacent tissues. We also investigated changes in the TTPs methylation status under temozolomide and doxorubicin treatment in MCF-7 cell line and found that temozolomide decreased TTPs methylation, which can potentially improve patient prognosis. In contrast, another well-known anticancer agent, doxorubicin, promoted TTPs methylation, which may impair an expected therapeutic effect of this drug.

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