Effects of the BET Bromodomain Inhibitor OTX015 on Epithelial–Mesenchymal Transition in Human Pancreatic Cancer Cells

Background This study aimed to explore the role of the bromodomain and extraterminal (BET) inhibitor OTX015 in pancreatic cancer cells and to investigate the potential mechanisms underlying its association with epithelial–mesenchymal transition (EMT). Methods Pancreatic cancer cells were treated with different small‐molecule inhibitors, alone or in combination with gemcitabine. The expression of the EMT marker protein vimentin and the extent of apoptosis were assessed by flow cytometry. High‐throughput sequencing was conducted to profile mRNA and miRNA expression changes in cells treated with OTX015 alone or in combination with gemcitabine. Bioinformatics analyses were subsequently performed to identify functional enrichment patterns and to construct mRNA–miRNA regulatory networks. Results OTX015 treatment was associated with increased vimentin expression in pancreatic cancer cells. The addition of gemcitabine attenuated EMT‐related changes without a corresponding increase in apoptosis. Transcriptomic analyses suggested that these effects may be linked to alterations in three specific miRNAs. Conclusion The BET bromodomain inhibitor OTX015 is associated with EMT‐related alterations in pancreatic cancer cells, potentially mediated through miRNA‐dependent regulatory mechanisms.