Prostate cancer (PCa) is the second leading cause of death from cancer in men. The mechanism underlying tumorigenesis and development of PCa is largely unknown. Here, we identified Kinesin family member 14 (KIF14) as a novel candidate oncogene in PCa. We found that KIF14 was overexpressed in multiple PCa cell lines and primary PCa tissues. Knockdown of KIF14 in DU145 and PC3 prostate cancer cells suppressed cell proliferation, induced cell cycle arrest and apoptosis. Transcriptome analysis by RNA-sequencing demonstrated that KIF4 suppression led to transcriptional changes of genes involved in p53 and TGF-beta signaling pathway. In addition, upregulated expression of GADD45A, GADD45B, p21, PIDD and Shisa5, which contribute to growth arrest and apoptosis induction, and downregulated CCNB1 that promotes cell cycle progression were confirmed by quantitative real-time PCR after KIF4 knockdown. We further found that KIF14 protein level was positively correlated with T stage and Gleason Score. Patients with higher KIF14 expression had shorter overall survival time than those with lower KIF14 expression. Thus, our data indicate that KIF14 could act as a potential oncogene that contributes to tumor progression and poor prognosis in PCa, which may represent a novel and useful prognostic biomarker for PCa.
Oncotarget. 2017 May 02 [Epub ahead of print]
Yixiang Zhang, Yeqing Yuan, Pei Liang, Zhaoxia Zhang, Xiaojing Guo, Ligang Xia, Yingying Zhao, Xing-Sheng Shu, Shengkun Sun, Ying Ying, Yingduan Cheng
Department of Urology, The Second Affiliated Hospital of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, People's Republic of China., Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA., Department of Pediatrics, The Second Affiliated Hospital of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, People's Republic of China., Department of Pathology, The Second Affiliated Hospital of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, People's Republic of China., Department of Gastrointestinal surgery, The Second Affiliated Hospital of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, People's Republic of China., Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen, Guangdong, China., Institute of Molecular Medicine, Health Science Center, Shenzhen University, Shenzhen, Guangdong, China., Department of Urology, Chinese PLA General Hospital, Beijing, China.