Open Access
ARTICLE
KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway
YONGLI WANG1,2,#, SHENHONG QU2,#, YONG YANG1, YING QIN2, FEI LIU3, GUANGWU HUANG1,*
1 Department of Otolaryngology & Head and Neck, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
2 Department of Otolaryngology & Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, China
3 Research Center of Medical Sciences, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
* Corresponding Author: GUANGWU HUANG. Email:
(This article belongs to this Special Issue: )
BIOCELL 2023, 47(3), 533-545. https://doi.org/10.32604/biocell.2023.025280
Received 06 July 2022; Accepted 13 September 2022; Issue published 03 January 2023
Abstract
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-α could 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.
Keywords
Cite This Article
, Y., QU, S., YANG, Y., QIN, Y., LIU, F. et al. (2023). KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway.
BIOCELL, 47(3), 533–545. https://doi.org/10.32604/biocell.2023.025280