The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At present, there is no well-established targeted drug for majority of patients. The kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and is dysregulated in multiple cancers. The objectives of this study were to evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate its biological functions in MB pathogenesis. By quantitative RT-PCR and immunohistochemistry, we found KIF14 was overexpressed in MB. Increased KIF14 expression at protein level was strongly associated with shorter progression-free survival (P=0.0063) and overall survival (P=0.0083). Fluorescence in situ hybridization (FISH) analysis confirmed genomic gain of chromosome 1q in 17/93 (18.3%) of MB. Combined genetic and immunohistochemical analyses revealed that 76.5% of MB with 1q gain showed consistent overexpression of KIF14, and a tight link between chromosome 1q gain and KIF14 overexpression (P=0.03). Transient, siRNAs-mediated downregulation of KIF14 suppressed cell proliferation and induced apoptosis in two MB cell lines. Stably KIF14 knockdown by shRNAs inhibited cell viability, colony formation, migration and invasion, and tumor sphere formation in MB cells. We conclude that KIF14 is dysregulated in MB and is an adverse prognostic factor for survival. Furthermore, KIF14 is part of MB biology and is a potential therapeutic target for MB.

Prognostic Prediction Using a Stemness Index-Related Signature in a Cohort of Gastric Cancer

“…Yang et al linked the upregulation of KIF14 in GC to poor prognosis, suggesting that it could play a critical function in GC pathogenesis ( Yang et al, 2019 ). In addition, KIF14 has been reported to serve oncogenic roles in a variety of malignancies such as colorectal cancer ( Wang et al, 2018 ), medulloblastoma ( Li et al, 2017 ), cervical cancer ( Wang et al, 2016 ). Moreover, KIF15 played a critical role in inhibiting GC cell apoptosis and promoting cell proliferation, and the high expression of KIF15 predicts a poor prognosis in GC patients ( Ding et al, 2020 ).…”

Whole‐exome sequencing revealed mutational profiles of giant cell glioblastomas

“…We further examined SETD2 and H3K36me3 levels by immunohistochemistry in our cohort. We adopted a semiquantitative scoring system in which signal intensity and percentage of positive cells were considered as parameters in grading IHC staining result . We found SETD2 expression level was not significantly different between SETD2‐wild‐type and SETD2‐mutant tumors.…”

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

“…Finally, KIF14 expression was found to be significantly elevated in 7 medulloblastoma cell lines and 32/32 human medulloblastoma tumor samples [64] . Analysis on a separate group of 93 medulloblastoma samples demonstrated that, as in glioma, greater KIF14 expression corresponded to shorter progression-free survival and overall survival.…”