Tristetraproline in breast cancer: treat or trick?

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.