Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma.
Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma.
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DOI：
10.1186/s13046-014-0061-1
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发表时间：
2014-07-25
期刊：
影响因子：
--
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Hu ZY;Yuan SX;Yang Y;Zhou WP;Jiang H
核转运蛋白α 2（KPNA 2）促进肝细胞癌（HCC）的肿瘤生长。我们的目的是确定的内容和临床意义的机制。通过免疫共沉淀法研究了转录因子多形性腺瘤基因1（PLAG 1）与KPNA 2的关系。建立体外功能获得和丧失模型以探索功能相互作用。应用314例肝癌患者的临床标本，探讨其临床意义。我们发现PLAG 1可以与KPNA 2结合，并被KPNA 2促进进入细胞核。PLAG 1抑制剂可显著抑制KPNA 2过表达引起的增殖和转移能力的增加。在临床样品中观察到KPNA 2和PLAG 1在细胞核中的共富集，并且可以区分具有最差预后的患者。PLAG 1阳性表达是无复发生存期（HR：1.766，1.315-2.371; P = 0.000）和总生存期（HR：1.589，1.138-2.220; P = 0.007）的独立危险因素。特别是对于KPNA 2染色阳性的患者（N = 152），PLAG 1阳性表达是无复发生存期（HR：1.749，1.146-2.670; P = 0.010）和总生存期（HR：1.662，1.007-2.744; P = 0.047）的唯一危险因素。PLAG 1通过KPNA 2的核输入对于KPNA 2在HCC细胞中的作用是必不可少的，并且对于预测HCC患者肝切除术后的不良存活率具有重要意义。
Karyopherin alpha 2 (KPNA2) promotes tumor growth in hepatocellular carcinoma (HCC). We aimed to determine the content and clinical significance of mechanism underlying. The association of transcriptional factor pleomorphic adenoma gene 1 (PLAG1) with KPNA2 was explored by co-immunoprecipitation. In vitro gain- and loss-of-function models were established to explore the functional interaction. Clinical samples from 314 HCC patients were applied to explore the clinical significance. We found that PLAG1 could associate with KPNA2 and be promoted into nucleus by KPNA2. The increment of proliferative and metastatic abilities by KPNA2 over-expression can be significantly retarded by PLAG1 inhibition. The co-enrichment of KPNA2 and PLAG1 in nucleus is observed in clinical samples and can distinguish patients with the worst prognosis. The positive PLAG1 expression is an independent risk factor of recurrence free survival (HR: 1.766, 1.315-2.371; P = 0.000) and overall survival (HR: 1.589, 1.138-2.220; P = 0.007). Especially for patients with positive KPNA2 staining (N = 152), the positive PLAG1 expression is the sole risk factor for both recurrence free survival (HR: 1.749, 1.146-2.670; P = 0.010) and overall survival (HR: 1.662, 1.007-2.744; P = 0.047). The nuclear import of PLAG1 by KPNA2 is essential for the role of KPNA2 in HCC cells and is significant to predict poor survival of HCC patients after hepatectomy.
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DOI：
10.1186/1756-9966-32-21
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期刊：
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