Regulation BRD4 by EF2-kinase and their role in tumorigenesis and treatment of breast cancer

Objective: Breast cancer is the most common type of cancer in women in the world. eEF2K is an alpha kinase that regulates cell cycle, migration and invasion in breast cancer. BRD4 is a member of the BET family; RNA activates polymerase II. In our hypothesis whether there was any relationship between eEF2K and BRD4. We aimed to clarify how the inhibition of BRD4 is affected by proliferation, migration and invasion in breast cancer cells. Method: In our study, we were used MDA-MB-231 cells. BRD4 inhibition was achieved with appropriate siRNAs and miR 122 in MDA-MB-231 cells. After the BRD4 inhibition; we performed MTS test for change in cell proliferation; clonogenic assay to evaluate colony formation. Invasion and migration analyzes were performed to explain the metastatic properties of the cells. Results: Our results showed that eEF2K does not directly affect BRD4. For BRD4 inhibition, it was decided to use appropriate siRNAs and miR 122. After BRD4 inhibition, BRD4 siRNAs reduced colony formation, invasion and migration in tumor cells. Furthermore, miR 122 was shown to provide inhibition, although not as effective as BRD4 siRNAs. Conclusion: miR 122 inhibits BRD4, and this inhibition slows colony formation, migration and invasion in the triple negative breast cancer cell line. Our results suggest that, inhibition of BRD4 with miR 122 could create a new treatment approach in aggressive metastatic breast cancers.