KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.