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蛋白酪氨酸磷酸酶N9(PTPN9)表达下调促进人肝细胞癌的生长和进展。

Downregulated Expression of PTPN9 Contributes to Human Hepatocellular Carcinoma Growth and Progression.

作者信息

Hu Baoying, Yan Xia, Liu Fang, Zhu Changlai, Zhou Huiling, Chen Yuyan, Liu Jinxia, Gu Xingxing, Ni Runzhou, Zhang Tianyi

机构信息

Basic Medic Research Centre, Medical College, Nantong University, Nantong, 226001, People's Republic of China.

Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.

出版信息

Pathol Oncol Res. 2016 Jul;22(3):555-65. doi: 10.1007/s12253-015-0038-1. Epub 2015 Dec 29.

DOI:10.1007/s12253-015-0038-1
PMID:26715439
Abstract

Human hepatocellular carcinoma (HCC) is one of the most common malignant cancers, whose molecular mechanisms is remains largely. PTPN9 has recently been reported to play a critical role in breast cancer development. However, the role of PTPN9 in human HCC remains elusive. The present study aimed at investigating the potential role of PTPN9 in HCC. Western blot and immunohistochemistry were used to examine the expression of PTPN9 protein in HCC and adjacent non-tumorous tissues in 45 patients. Furthermore, Cell Counting Kit-8, flow cytometry and RNA interference experiments were performed to analyze the role of PTPN9 in the regulation of HCC cell proliferation. We showed that the expression level of PTPN9 was significantly reduced in HCC, compared with adjacent non-tumorous tissues. PTPN9 expression was inversely associated with Tumor size (P = 0.014), serum AFP level (P = 0.004) and Ki-67 expression. Low expression of PTPN9 predicted poor survival in HCC patients. Moreover, PTPN9 interference assay that PTPN9 inhibited cell proliferation in HepG2 cells. Cell apoptosis assay revealed that, silencing of PTPN9 expression significantly reduced cell apoptosis, compared with control ShRNA treatment group. Our results suggested that PTPN9 expression was down-regulated in HCC tumor tissues, and reduced PTPN9 expression was associated with worsened overall survival in HCC patients. Depletion of PTPN9 inhibits the apoptosis and promotes the proliferation of HCC cells.

摘要

人类肝细胞癌(HCC)是最常见的恶性肿瘤之一,其分子机制在很大程度上仍不清楚。最近有报道称PTPN9在乳腺癌发展中起关键作用。然而,PTPN9在人类HCC中的作用仍然难以捉摸。本研究旨在探讨PTPN9在HCC中的潜在作用。采用蛋白质免疫印迹法和免疫组织化学法检测45例HCC患者及其癌旁非肿瘤组织中PTPN9蛋白的表达。此外,进行细胞计数试剂盒-8、流式细胞术和RNA干扰实验,以分析PTPN9在调节HCC细胞增殖中的作用。我们发现,与癌旁非肿瘤组织相比,HCC中PTPN9的表达水平显著降低。PTPN9表达与肿瘤大小(P = 0.014)、血清甲胎蛋白水平(P = 0.004)和Ki-67表达呈负相关。PTPN9低表达预示着HCC患者的生存预后较差。此外,PTPN9干扰试验表明PTPN9抑制HepG2细胞的增殖。细胞凋亡试验显示,与对照短发夹RNA处理组相比,PTPN9表达沉默显著降低细胞凋亡。我们的结果表明,HCC肿瘤组织中PTPN9表达下调,PTPN9表达降低与HCC患者总体生存率恶化相关。PTPN9的缺失抑制HCC细胞的凋亡并促进其增殖。

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Downregulated Expression of PTPN9 Contributes to Human Hepatocellular Carcinoma Growth and Progression.蛋白酪氨酸磷酸酶N9(PTPN9)表达下调促进人肝细胞癌的生长和进展。
Pathol Oncol Res. 2016 Jul;22(3):555-65. doi: 10.1007/s12253-015-0038-1. Epub 2015 Dec 29.
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本文引用的文献

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MIF4G domain containing protein regulates cell cycle and hepatic carcinogenesis by antagonizing CDK2-dependent p27 stability.MIF4G 结构域包含蛋白通过拮抗 CDK2 依赖性 p27 稳定性来调节细胞周期和肝肿瘤发生。
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Fc receptor-like 1, 3, and 6 variants are associated with rheumatoid arthritis risk in the Chinese Han population.
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PTPN9 induces cell apoptosis by mitigating the activation of Stat3 and acts as a tumor suppressor in colorectal cancer.PTPN9通过减轻Stat3的激活来诱导细胞凋亡,并在结直肠癌中作为一种肿瘤抑制因子发挥作用。
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MiR-96 enhances cellular proliferation and tumorigenicity of human cervical carcinoma cells through PTPN9.微小RNA-96通过蛋白酪氨酸磷酸酶非受体型9增强人宫颈癌细胞的细胞增殖能力和致瘤性。
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PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126.蛋白酪氨酸磷酸酶N9促进Eca109细胞的增殖和侵袭,并受到微小RNA-126的负调控。
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MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling.
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Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and activator of transcription 3 and suppresses tumor growth in breast cancer.蛋白酪氨酸磷酸酶 Meg2 去磷酸化信号转导子和转录激活子 3,并抑制乳腺癌中的肿瘤生长。
Breast Cancer Res. 2012 Mar 6;14(2):R38. doi: 10.1186/bcr3134.
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Hepatocellular carcinoma.肝细胞癌
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PTP1B suppresses prolactin activation of Stat5 in breast cancer cells.PTP1B 抑制乳腺癌细胞中催乳素激活 Stat5。
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