USP14 promotes the malignant progression and ibrutinib resistance of mantle cell lymphoma by stabilizing XPO1

Background: Mantle cell lymphoma (MCL) is a heterogeneous disease belonging to non-Hodgkin's lymphoma. In recent years, the morbidity rate of MCL is ascending, and the prognosis remains unfavorable. Ubiquitin-specific proteases14 (USP14) has been evidenced to be engaged in the process of malignant tumors. In this article, the role of USP14 in the malignant process of MCL and the mechanism of ibrutinib resistance were discussed. Methods: Through qRT-PCR and western blot, the mRNA and protein expressions of USP14 in MCL cells were tested. USP14 interference plasmid was constructed by cell transfection technology, and then CCK8 and EdU assays were applied to appraise cell proliferation. Cell cycle and cell apoptosis were estimated by flow cytometry and western blot. The sensitivity of MCL cells to ibrutinib was also investigated. Next, western blot, co-IP, Cycloheximide (CHX) assay and other techniques were used to detect the relationship between USP14 and XPO1. Finally, by simultaneously inhibiting USP14 and overexpressing XPO1, the impacts of USP14 on the malignant process of MCL and the regulatory mechanism of ibrutinib sensitivity in MCL were discussed. Results: USP14 expression was markedly fortified in MCL cell lines. Interference of USP14 suppressed MCL cell viability, potentiated cell cycle arrest, apoptosis, and ibrutinib sensitivity. This process might be achieved by USP14 deubiquitination through enhancing XPO1 stability. Conclusion: USP14 can promote the malignant progression and ibrutinib sensitivity of MCL by stabilizing XPO1.