KIF15 Accelerated The Progression of Nasopharyngeal Carcinoma and Predict Poor Prognosis

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a common tumor in head and neck and is prevailing in China. Although treatment methods continue to improve, the prognosis of advanced patients is still unsatisfactory. Kinesin family member 15 (KIF15) is a kind of protein, which regulates the process of cell mitosis and plays an important role in several types of human cancers. This study aims to investigate the role of KIF15 in NPC.Methods: First, the differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on both data collected from Gene Expression Omnibus (GEO) database and immunohistochemical analysis on clinical specimens collected from in-house cohort. Next, cell lines C666-1 and CNE-2Z were selected for the construction of KIF15‑knockdown cell models. Then, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, wound healing, Transwell and clone formation assays were used to detect the proliferation, apoptosis, migration, invasion and colony formation of nasopharyngeal carcinoma cells in vitro. A mouse xenograft model was constructed for in vivo study. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in NPC. In the end, the potential molecular mechanisms underlying the effects of KIF15 was explored through western blot analysis.Results: The results showed that the expression of KIF15 in NPC tissues is higher than that in para-carcinoma tissues, and high levels of KIF15 expression are associated with low survival rates. In addition, knockdown of KIF15 inhibited cell proliferation, migration, invasion and colony formation ability, and promoted cell apoptosis. What’s more, in vivo xenograft experiments showed that down-regulation of KIF15 can inhibit NPC tumor growth. Moreover, the mechanism study demonstrated a variety of apoptosis-related proteins as well as PI3K/AKT and MAPK signaling pathways may be involved in KIF15-induced regulation of NPC.Conclusions: In short, we demonstrated that KIF15 is overexpressed and accelerated the progression of nasopharyngeal carcinoma. It can be used as a new prognostic indicator as well as a potential drug target for the treatment of NPC.