上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

抑制JAK2/STAT3信号通路对肺癌细胞A549中HIF-1α、VEGF和miRNA-145表达的影响

伊庆强1,2，赵 美1，王炯轶1，孔飞飞1，袁海花1，王美玲1，姜 斌1   

  1. 1.上海交通大学 医学院附属第三人民医院肿瘤科, 上海 201999; 2.蚌埠医学院 研究生部，蚌埠 233000
  • 出版日期:2014-07-28 发布日期:2014-08-11
  • 通讯作者: 姜 斌, 电子信箱: Dr_jiangbin@yeah.net。
  • 作者简介:伊庆强(1981—)， 男， 主治医师， 硕士生; 电子信箱: yi_qingqiang@126.com。
  • 基金资助:

    上海交通大学医学院科技基金（11XJ22014）；上海交通大学医学院附属第三人民医院院基金（syz2011-05）；上海市教委优青项目（zzjdyx12111）

Effects of inhibiting JAK2/STAT3 signaling pathway on expressions of HIF-1α, VEGF, and miRNA-145 of A549 lung cells

YI Qing-qiang1,2, ZHAO Mei1, WANG Jiong-yi1, KONG Fei-fei1, YUAN Hai-hua1, WANG Mei-ling1, JIANG Bin1   

  1. 1.Department of Oncology, the Third People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999； 2.Bengbu Medical College Graduate Department, Bengbu 233000, China
  • Online:2014-07-28 Published:2014-08-11
  • Supported by:

    Science and Technology Foundation of Shanghai Jiao Tong University School of Medicine,11XJ22014; Foundation of the Third People's Hospital, Shanghai Jiao Tong University School of Medicine, syz2011-05; Excellent Young Talents Project of Shanghai Municipal Education Committee, zzjdyx12111

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摘要：

目的 探讨抑制Janus蛋白酪氨酸激酶2 (JAK2)/信号转导和转录激活子3 (STAT3)信号通路对人肺腺癌细胞株A549中缺氧诱导因子-1α (HIF-1α)、血管内皮生长因子（VEGF）和微RNA145 （miRNA-145）表达的影响。方法 采用Western blotting和RT-PCR技术检测经不同浓度Jak2/STAT3特异性抑制剂AG490处理或转染靶向STAT干扰小RNA (siRNA)A549细胞（AG490组和siRNA-STAT组）中HIF-1α、VEGF和miRNA-145蛋白和mRNA的表达变化。以未经AG490处理及未转染细胞作为空白对照组，转染无关序列siRNA细胞作为阴性对照组。结果 与空白对照组比较，AG490组A549细胞中miRNA-145的表达显著上调（P<0.05），HIF-1α 和VEGF蛋白和mRNA的表达随着AG490浓度的增高而逐渐降低。与空白对照组和阴性对照组比较，siRNA-STAT组A549细胞中STAT3蛋白、磷酸化STAT3蛋白的表达及HIF-1α、VEGF mRNA的表达明显下调，而miRNA145的表达显著升高（P<0.05）。结论 在人肺腺癌细胞A549中，抑制JAK2/STAT3信号通路可使miRNA-145的表达上调，而HIF-1α和VEGF的表达下调。

关键词: Janus蛋白酪氨酸激酶2/信号转导和转录激活子3, 缺氧诱导因子-1α, 血管内皮生长因子, 微RNA145

Abstract:

Objective To explore the effects of the inhibition of Janus kinase 2/signal transducers and activator of transcription 3 (JAK2/STAT3) on the expression of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and microRNA-145 (miRNA-145) in A549 lung cancer cell line. Methods The  expressions of HIF-1α, VEGF, and miRNA-145 protein and mRNA in A549 cells were detected by the Western blotting and RT-PCR after being treated by Jak2/STAT3 specific inhibitor AG490 of different concentrations (the AG490 group) or transfected by siRNA targeting to STAT (the siRNA-STAT group). Cells of the blank control group were not treated by AG490 or transfected. Cells of the negative control group were siRNA cells of sequences irrelevant to the transfection. Results Compared to the blank control group, the expression of miRNA-145 of A549 cells of the AG490 group up-regulated significantly (P<0.05) and the expressions of HIF-1α and VEGF protein and mRNA gradually decreased with the increase of the concentration of AG490. Compared to the blank control group and negative control group, the expressions of STAT3, phosphorylated STAT3, HIF-1α, and VEGF mRNA of A549 cells of the siRNA-STAT group down-regulated significantly, while the expression of miRNA145 increased significantly (P<0.05). Conclusion The inhibition of JAK2/STAT3 signaling pathway of A549 human lung adenocarcinoma cell can up-regulate the expression of miRNA-145 and down-regulate the expressions of HIF-1α and VEGF.

Key words: Janus kinase 2/signal transducers and activator of transcription 3, hypoxia inducible factor-1α, vascular endothelial growth factor, microRNA-145