Targeting DUSP5 suppresses malignant phenotypes of BRAF-mutant thyroid cancer cells and improves their response to sorafenib.

Purpose: The role of dual-specificity phosphatase-5 (DUSP5) in BRAF-mutant thyroid cancers remains unclear. The aims of this study are to investigate the role of DUSP5 in BRAF-mutant thyroid cancer cells, explore its value in the diagnosis and evaluate therapeutic potential of targeting DUSP5 combined with sorafenib for BRAF-mutant thyroid cancer patients.
Methods: The role of DUSP5 in thyroid cancer cells was determined by a series of in vitro and in vivo experiments. Underlying mechanisms were explored by western blotting analysis. The diagnostic value of combination detection of DUSP5 expression and BRAF ^V600E mutation was evaluated using ROC curve.
Results: Knocking down DUSP5 in BRAF-mutant thyroid cancer cells significantly inhibited colony formation, cell migration and invasion, meanwhile, induced cell cycle arrest and cell apoptosis. Moreover, inhibition of DUSP5 improved the anti-tumor efficacy of sorafenib both in vitro and in vivo. Besides, combination detection of DUSP5 expression and BRAF ^V600E mutation showed much more accuracy in preoperative diagnosis of thyroid cancer.
Conclusions: Our data demonstrate an oncogenic role of DUSP5 in BRAF-mutant thyroid cancer cells, and combined analysis of its expression and BRAF ^V600E mutation can accurately diagnose thyroid cancer. In addition, inhibition of DUSP5 improves the response of BRAF-mutant thyroid cancer cells to sorafenib.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)