Overexpression of a novel candidate oncogene KIF14 correlates with tumor progression and poor prognosis in prostate cancer

被引:42
|
作者
Zhang, Yixiang [1 ]
Yuan, Yeqing [1 ]
Liang, Pei [2 ]
Zhang, Zhaoxia [3 ]
Guo, Xiaojing [4 ]
Xia, Ligang [5 ]
Zhao, Yingying [6 ]
Shu, Xing-Sheng [7 ]
Sun, Shengkun [8 ]
Ying, Ying [6 ]
Cheng, Yingduan [1 ]
机构
[1] Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 2, Dept Urol, Shenzhen, Guangdong, Peoples R China
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA
[3] Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 2, Dept Pediat, Shenzhen, Guangdong, Peoples R China
[4] Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 2, Dept Pathol, Shenzhen, Guangdong, Peoples R China
[5] Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 2, Dept Gastrointestinal Surg, Shenzhen, Guangdong, Peoples R China
[6] Shenzhen Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Physiol, Shenzhen, Guangdong, Peoples R China
[7] Shenzhen Univ, Hlth Sci Ctr, Inst Mol Med, Shenzhen, Guangdong, Peoples R China
[8] Chinese Peoples Liberat Army Gen Hosp, Dept Urol, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
KIF14; prostate cancer; apoptosis; proliferation; G2; arrest; FAMILY-MEMBER; 14; CELL GROWTH; PROTEIN; EXPRESSION; SUPPRESSOR; GENE; PROLIFERATION; CARCINOMA; SCOTIN; MARKER;
D O I
10.18632/oncotarget.17564
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:45459 / 45469
页数:11
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