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高 Annexin A5 表达促进肾细胞癌的肿瘤进展和不良预后。

High Annexin A5 expression promotes tumor progression and poor prognosis in renal cell carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.

出版信息

Int J Oncol. 2017 May;50(5):1839-1847. doi: 10.3892/ijo.2017.3942. Epub 2017 Apr 3.

Abstract

Annexin A5 has been found to act as an oncogenic protein in a variety of cancers. However, its specific biological role and mechanism in renal cell cancer (RCC) remains unknown. Quantitative Real-time PCR and western blotting were used to evaluate the mRNA and protein expression level of Annexin A5 in human RCC cell lines and tissues. Immunohistochemistry was adopted to measure the Annexin A5 expression in 123 cases of RCC tissues. Survival analysis was performed to explore the association between Annexin A5 expression and the prognosis of RCC. The effect of Annexin A5 on RCC growth and metastasis was studied in vitro and in vivo. Annexin A5 was frequently highly expressed in both human RCC cells and tissues. High Annexin A5 expression was associated with higher clinical stage and histological grade. In addition, Annexin A5 might be used as a predictive factor for the prognosis of RCC. Further research suggested that upregulated Annexin A5 in RCC cells could significantly promote tumor cell proliferation, migration and invasion in vitro. Subcutaneous xenograft tumor model displayed that knockdown of Annexin A5 could impede tumorigenesis in vivo. Moreover, mechanism study exhibited that Annexin A5 could activate PI3K/Akt/mTOR signaling pathway, promote epithelial-mesenchymal transition (EMT) and the expression of MMP2 and MMP9. Annexin A5 may be a potential prognostic biomarker in RCC and promotes proliferation, migration and invasion of RCC cells via activating PI3K/Akt/mTOR signaling pathway and regulating EMT process and MMP expression.

摘要

膜联蛋白 A5 已被发现作为多种癌症中的致癌蛋白。然而,其在肾细胞癌(RCC)中的具体生物学作用和机制仍不清楚。本研究采用实时定量 PCR 和 Western blot 检测 Annexin A5 在人 RCC 细胞系和组织中的 mRNA 和蛋白表达水平,采用免疫组织化学法检测 123 例 RCC 组织中 Annexin A5 的表达,生存分析探索 Annexin A5 表达与 RCC 预后的关系,体外和体内实验研究 Annexin A5 对 RCC 生长和转移的影响。结果表明,膜联蛋白 A5 在人 RCC 细胞和组织中均频繁高表达,高 Annexin A5 表达与较高的临床分期和组织学分级相关,可能作为 RCC 预后的预测因子。进一步研究表明,RCC 细胞中上调的 Annexin A5 可显著促进肿瘤细胞在体外的增殖、迁移和侵袭,皮下移植瘤模型显示 Annexin A5 敲低可抑制体内肿瘤发生。此外,机制研究表明 Annexin A5 可激活 PI3K/Akt/mTOR 信号通路,促进上皮-间充质转化(EMT)和 MMP2、MMP9 的表达。膜联蛋白 A5 可能是 RCC 潜在的预后生物标志物,通过激活 PI3K/Akt/mTOR 信号通路和调节 EMT 过程及 MMP 表达,促进 RCC 细胞的增殖、迁移和侵袭。

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