HJURP promotes proliferation in prostate cancer cells through increasing CDKN1A degradation via the GSK3β/JNK signaling pathway.

HJURP promotes proliferation in prostate cancer cells through increasing CDKN1A degradation via the GSK3β/JNK signaling pathway.
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HJURP 通过 GSK3β/JNK 信号通路增加 CDKN1A 降解,促进前列腺癌细胞增殖

DOI:
10.1038/s41419-021-03870-x
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发表时间:
2021-06-07
影响因子:
9
通讯作者:
Wen X
Wen X
中科院分区:
生物学1区
文献类型:
--
作者:
Lai W;Zhu W;Xiao C;Li X;Wang Y;Han Y;Zheng J;Li Y;Li M;Wen X

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具有跨癌种异常的基因极有可能是功能基因或潜在的治疗靶点。在此,我们发现共有137个基因在8种癌症类型中异位表达,其中霍利迪连接体识别蛋白(HJURP)在前列腺癌(PCa)中显著上调。此外,HJURP信使核糖核酸(mRNA)和蛋白水平较高的患者预后较差,且蛋白水平是前列腺癌患者总生存期的一个独立预后因素。从功能上看,异位的HJURP表达在体外和体内均促进了前列腺癌细胞的增殖。从机制上讲,HJURP通过糖原合成酶激酶3β(GSK3β)/c-Jun氨基末端激酶(JNK)信号通路增加细胞周期蛋白依赖性激酶抑制剂1(CDKN1A)的泛素化,并降低其稳定性。本研究探究了HJURP在前列腺癌增殖中的作用,可能为前列腺癌提供一个新的预后和治疗靶点。
Genes with cross-cancer aberrations are most likely to be functional genes or potential therapeutic targets. Here, we found a total of 137 genes were ectopically expressed in eight cancer types, of which Holliday junction recognition protein (HJURP) was significantly upregulated in prostate cancer (PCa). Moreover, patients with higher HJURP mRNA and protein levels had poorer outcomes, and the protein levels served as an independent prognosis factor for the overall survival of PCa patients. Functionally, ectopic HJURP expression promoted PCa cells proliferation in vitro and in vivo. Mechanistically, HJURP increased the ubiquitination of cyclin-dependent kinase inhibitor 1 (CDKN1A) via the GSK3β/JNK signaling pathway and decreased its stability. This study investigated the role of HJURP in PCa proliferation and may provide a novel prognostic and therapeutic target for PCa.
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