Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells
Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells
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DOI：
10.1016/j.canlet.2019.02.005
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Khan, Shafiq
中科院分区：
文献类型：
--
作者：
Elliott, Bethtrice;Millena, Ana Cecilia;Khan, Shafiq
JunD是AP-1家族的成员，对前列腺癌（PCa）细胞的细胞增殖至关重要。我们最近证实，在PCa细胞中敲低JunD（KD）导致细胞周期停滞在G（1）期，伴随着细胞周期蛋白D1、Ki 67和c-MYC的减少，但p21水平增加。此外，JunD的过表达显著增加增殖，表明JunD调节细胞周期进程所需的基因。在这里，采用基因表达谱，定量蛋白质组学和验证方法，我们证明了JunD KD与不同的基因和蛋白质表达模式相关。通过免疫途径分析（IPA）进行的比较整合分析鉴定了1）细胞周期控制/调节作为顶级经典途径，其成员在JunD KD后表现出其表达的显著降低，包括PRDX 3、PEA 15、KIF 2C和CDK 2，和2）JunD依赖性基因与细胞增殖相关，MYC作为关键下游调节因子。相反，JunD过表达诱导包括c-MYC在内的上述基因的表达。我们的结论是，JunD是细胞周期进程的重要调节因子，抑制其靶基因可能是阻断前列腺癌发生的有效方法。
JunD, a member of the AP-1 family, is essential for cell proliferation in prostate cancer (PCa) cells. We recently demonstrated that JunD knock-down (KD) in PCa cells results in cell cycle arrest in G(1)-phase concomitant with a decrease in cyclin D1, Ki67, and c-MYC, but an increase in p21 levels. Furthermore, the over-expression of JunD significantly increased proliferation suggesting JunD regulation of genes required for cell cycle progression. Here, employing gene expression profiling, quantitative proteomics, and validation approaches, we demonstrate that JunD KD is associated with distinct gene and protein expression patterns. Comparative integrative analysis by Ingenuity Pathway Analysis (IPA) identified 1) cell cycle control/regulation as the top canonical pathway whose members exhibited a significant decrease in their expression following JunD KD including PRDX3, PEA15, KIF2C, and CDK2, and 2) JunD dependent genes are associated with cell proliferation, with MYC as the critical downstream regulator. Conversely, JunD over-expression induced the expression of the above genes including c-MYC. We conclude that JunD is a crucial regulator of cell cycle progression and inhibiting its target genes may be an effective approach to block prostate carcinogenesis.