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

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 multipl...

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Veröffentlicht in:Oncotarget 2017-07, Vol.8 (28), p.45459-45469
Hauptverfasser: Zhang, Yixiang, Yuan, Yeqing, Liang, Pei, Zhang, Zhaoxia, Guo, Xiaojing, Xia, Ligang, Zhao, Yingying, Shu, Xing-Sheng, Sun, Shengkun, Ying, Ying, Cheng, Yingduan
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container_end_page 45469
container_issue 28
container_start_page 45459
container_title Oncotarget
container_volume 8
creator Zhang, Yixiang
Yuan, Yeqing
Liang, Pei
Zhang, Zhaoxia
Guo, Xiaojing
Xia, Ligang
Zhao, Yingying
Shu, Xing-Sheng
Sun, Shengkun
Ying, Ying
Cheng, Yingduan
description 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.
doi_str_mv 10.18632/oncotarget.17564
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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. 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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. 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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.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28525372</pmid><doi>10.18632/oncotarget.17564</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Apoptosis - genetics
Biomarkers, Tumor
Cell Line, Tumor
Cell Proliferation
Computational Biology - methods
Disease Progression
G2 Phase Cell Cycle Checkpoints - genetics
Gene Expression
Gene Expression Profiling
Gene Knockdown Techniques
Humans
Kinesin - genetics
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Oncogene Proteins - genetics
Oncogenes
Prognosis
Prostatic Neoplasms - genetics
Prostatic Neoplasms - mortality
Prostatic Neoplasms - pathology
Research Paper
title Overexpression of a novel candidate oncogene KIF14 correlates with tumor progression and poor prognosis in prostate cancer
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