Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer.
Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer.
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异质核核糖核蛋白 K 与不良预后相关，并调节膀胱癌的增殖和凋亡。
DOI：
10.1111/jcmm.12999
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发表时间：
2017-07
影响因子：
5.3
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Chen X;Gu P;Xie R;Han J;Liu H;Wang B;Xie W;Xie W;Zhong G;Chen C;Xie S;Jiang N;Lin T;Huang J
异质核核糖核蛋白K （hnRNPK）是一种重要的RNA和DNA结合蛋白，调节多种生物事件，特别是DNA转录。hnRNPK过表达与几种癌症的肿瘤发生有关。然而，hnRNPK在膀胱癌中的表达模式和生物学机制尚不清楚。我们通过免疫组化方法对188例膀胱癌患者的hnRNPK表达进行了研究，发现hnRNPK在膀胱癌组织中表达水平显著升高，且高hnRNPK表达与预后不良密切相关。功能丧失和功能获得实验表明，hnRNPK在体外促进膀胱癌细胞的增殖、抗凋亡和化疗耐药，而在体内，hnRNPK敲低抑制了致瘤性。从机制上讲，hnRNPK通过直接介导细胞周期蛋白D1、G0/G1开关2 （G0S2）、XIAP相关因子1和ERCC切除修复4、核酸内切酶催化亚基（ERCC4）转录来调节膀胱癌的多种功能。综上所述，我们发现hnRNPK在膀胱癌中发挥重要作用，提示它是一种潜在的预后标志物，也是治疗膀胱癌的一个有希望的靶点。
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an essential RNA‐ and DNA‐binding protein that regulates diverse biological events, especially DNA transcription. hnRNPK overexpression is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of hnRNPK in bladder cancer are unclear. We investigated hnRNPK expression by immunohistochemistry in 188 patients with bladder cancer, and found that hnRNPK expression levels were significantly increased in bladder cancer tissues and that high‐hnRNPK expression was closely correlated with poor prognosis. Loss‐ and gain‐of‐function assays demonstrated that hnRNPK promoted proliferation, anti‐apoptosis, and chemoresistance in bladder cancer cells in vitro, and hnRNPK knockdown suppressed tumorigenicity in vivo. Mechanistically, hnRNPK regulated various functions in bladder cancer by directly mediating cyclin D1, G0/G1 switch 2 (G0S2), XIAP‐associated factor 1, and ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) transcription. In conclusion, we discovered that hnRNPK plays an important role in bladder cancer, suggesting that it is a potential prognostic marker and a promising target for treating bladder cancer.