Silencing FOXP2 reverses vemurafenib resistance in BRAF V600E mutant papillary thyroid cancer and melanoma cells

Background Vemurafenib (VEM) is a commonly used inhibitor of papillary thyroid cancer (PTC) and melanoma with the BRAF V600E mutation; however, acquired resistance is unavoidable. The present study aimed to identify a potential target to reverse resistance. Materials and methods A VEM-resistant PTC cell line (B-CPAP/VR) was established by gradually increasing the drug concentration, and a VEM-resistant BRAF V600E melanoma cell line (A375/VR) was also established. RNA sequencing and bioinformatics analyses were conducted to identify dysregulated genes and construct a transcription factor (TF) network. The role of a potential TF, forkhead box P2 (FOXP2), verified by qRT-PCR, was selected for further confirmation. Results The two resistant cell lines were tolerant of VEM and displayed higher migration and colony formation abilities ( p < 0.05). RNA sequencing identified 9177 dysregulated genes in the resistant cell lines, and a TF network consisting of 13 TFs and 44 target genes was constructed. Alterations in FOXP2 expression were determined to be consistent between the two VEM-resistant cell lines. Finally, silencing FOXP2 resulted in an increase in drug sensitivity and significant suppression of the migration and colony formation abilities of the two resistant cell lines ( p < 0.05). Conclusions The present study successfully established two VEM-resistant cell lines and identified a potential target for VEM-resistant PTC or melanoma.