Abstract
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.
Highlights
Prostate cancer (PCa) is one of the most commonly diagnosed malignant tumor and the second leading cause of cancer death among men in the United States
Based on analysis on two datasets derived from samples of patients with PCa [15, 16], we determined that Kinesin family member 14 (KIF14) is highly overexpressed in prostate carcinoma as compared with normal prostate tissues (Figure 1B)
In both DU145 and PC3 cells, knockdown of KIF14 upregulated the gene expression of GADD45A, GADD45B, p21, PIDD and Shisa5, which contribute to growth arrest and apoptosis induction, while downregulated CCNB1 that promotes cell cycle progression (Figure 4C and Figure 4D)
Summary
Prostate cancer (PCa) is one of the most commonly diagnosed malignant tumor and the second leading cause of cancer death among men in the United States. The kinesin family proteins (KIFs) are ATP- and microtubule-associated motor proteins involved in cell division, microtubule polymer dynamics, intracellular transportation and signal transduction [3]. KIF14 levels are prognostic for the outcome of hepatocellular carcinoma and ovarian cancer, where KIF14 overexpression enhances tumor growth, while its knockdown decreases tumorigenicity in vitro and in xenografts [13]. We further found that KIF14 expression was significantly upregulated in primary human PCa specimens. Our data indicate that KIF14 overexpression contributes to prostate tumor progression and is associated with poor prognosis for PCa patients, which could be served as a novel and useful prognostic indicator for PCa
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