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Trends in Cancer Research   Volumes    Volume 18 
Expressional regulations of EMT-associated transcription factors due to treatment with epigenetic agents in acute myeloid leukemia cells
Boubacar Balde, Ilayda Alcitepe, Burcin Tezcanlı Kaymaz
Pages: 39 - 50
Number of pages: 12
Trends in Cancer Research
Volume 18 

Copyright © 2023 Research Trends. All rights reserved

EMT plays a crucial role in both myeloid and lymphoid cancers and is regulated by HDACs and bromodomain proteins. The BRD4 inhibitor PLX51107 binds to lysine motifs acetylated in the bromodomains of BRD4. Vorinostat (SAHA) is an HDAC inhibitor that promotes protein acetylation, modulates gene expression, induces differentiation, and inhibits proliferation. This study aims to investigate the synergistic cytotoxic effect of Plx51107 and Vorinostat on myeloid leukemic cells (AML). The study evaluates the expression regulation of EMT-associated transcription factors (TF) in vitro by treating the AML cell line HL60 and the healthy B-lymphocyte cell line NCIBL2171 with mono- and synergistic combinations of Plx51107 and Vorinostat IC50 doses. The mRNA expression levels of EMT-related TFs were determined by qRT-PCR using Cfx Biorad software. Bioinformatic analysis using STRING (protein-protein interaction) analysis (PPI network) was performed to evaluate the interactions between EMT genes. The IC50 doses of Plx51107 and Vorinostat were 1.24 µM and 2.01 µM for NCIBL2171 cells, respectively. For HL60 cells, it was 6.68 µM for Plx51107 and 4.3 µM for Vorinostat. The synergistic combination dose was 10 µm Plx51107 and 4.3 µm Vorinostat. In HL60 cells, SNAI1,N-cadherin, Claudin, Zeb1, E-cadherin, SNAI2, and TWIST1 expressions decreased in both Plx51107 and Vorinostat-applied AML cells compared to untreated AML cells differing between 2-15.75 folds, whereas ZO-1, Zeb2, and VIM increased. As for NCIBL2171 cells, the expression of all target genes decreased in both Plx51107 and Vorinostat doses compared to their untreated counterparts. The search tool for the retrieval of ınteracting genes (STRING) analysis showed that the interactions of the EMT genes are defined by 44 edges involving 12 nodes. These nodes symbolize a protein and the edges symbolize protein-protein interactions. The STRING database enriches protein interactions, indicating biological connections within the group. The changes in the EMT-associated transcription factors following epigenetic treatment might indicate a therapeutic effect on the EMT transition. The use of the bromodomain inhibitör Plx51107 and HDAC inhibitör Vorinostat may be an effective strategy for the treatment of hematological malignancies and the determination of anti-proliferative activity in cancer cells, contributing to the development of clinical trials.
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