RASSF1A对黑色素瘤A375细胞基因网络的影响
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中南大学湘雅医院皮肤性病科,中南大学湘雅医院皮肤性病科,中南大学肿瘤研究所,中南大学湘雅医院皮肤性病科,中南大学湘雅医院皮肤性病科,中南大学肿瘤研究所,中南大学湘雅医院皮肤性病科,中南大学湘雅医院皮肤性病科,中南大学肿瘤研究所,中南大学湘雅医院皮肤性病科

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国家自然科学基金(81102065,81171930),教育部高等学校博士学科点基金(20110162120009),中南大学自由探索计划(201012200017,2011QNZT138)资助项目


Gene Network Modulated by RASSF1A Over-expression in Melanoma A375 Cells
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Department of Dermatology, Xiangya hospital of Central South University,Department of Dermatology, Xiangya hospital of Central South University,Cancer research institute of Central South University,Department of Dermatology, Xiangya hospital of Central South University,Department of Dermatology, Xiangya hospital of Central South University,cancer research institute, central south university,Department of Dermatology, Xiangya hospital of Central South University,Department of Dermatology, Xiangya hospital of Central South University,Cancer research institute of Central South University,Department of Dermatology, Xiangya hospital of Central South University

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This work was supported by grants from The National Natural Science Foundation of China(81102065, 81171930), Specialized Research Fund for the Doctoral Program of Higher Education (20110162120009) and The Free Exploration Program of Central South University of China(201012200017, 2011QNZT138)

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    摘要:

    RASSF1A (Ras association domain family 1 isoform A)是定位于染色体3p21.3区域的抑瘤基因,编码一个由340个氨基酸残基构成的微管相关蛋白.该基因在包括恶性黑色素瘤在内的多种肿瘤中因启动子高甲基化而表达沉默.本研究建立了RASSF1A稳定表达的恶性黑色素瘤A375细胞系,通过全基因组表达谱基因芯片分析RASSF1A过表达对A375细胞基因表达谱的影响,发现RASSF1A引起184个基因表达上调,26个基因表达下调.通过Realtime RT-PCR对部分差异表达基因进行验证,结果表明与芯片筛选结果一致.RASSF1A影响的差异表达基因功能上归属于细胞生长与增殖、细胞周期、细胞凋亡、细胞间黏附、信号传导等生物过程.采用STRING软件构建了RASSF1A影响的差异表达基因调控网络,结果表明RASSF1A调控的差异表达基因构成一个高连接度的基因网络.其中,炎症细胞因子、转录因子位于网络中央.RASSF1A通过影响炎症细胞因子与转录因子之间的表达,影响A375细胞基因网络,调节黑色素瘤恶性生物学行为.

    Abstract:

    Gene regulatory networks have an important role in every process of life, including cell differentiation, metabolism, the cell cycle and signal transduction. The RASSF1A is a tumor suppressor gene involved in several growth regulatory and pro-apoptotic pathways. In this study, we have used microarray technology to define differences in the gene expression profiles subsequent to exogenous wild-type RASSF1A in melanoma A375 cells. Gene expression changes were verified in a subset of genes using real time RT-PCR. Association of modulated genes with biological functional groups identified several pathways affected by RASSF1A including cell death, cellular growth and proliferation, and cellular development. GRN of modulated genes were identified using the STRING. Pro-inflammatory factors and transcription factors locates in the center of RASSF1A modulated gene regulatory networks. Our results suggested that RASSF1A might affect melanoma gene regulatory network via modulating the expression and interaction between pro-inflammatory factors and transcription factors.

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易梅,李吉,粟娟,张江林,陈翔,杜乾君,向波,熊炜,李小玲,谢红付. RASSF1A对黑色素瘤A375细胞基因网络的影响[J].生物化学与生物物理进展,2014,41(4):352-361

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历史
  • 收稿日期:2013-06-06
  • 最后修改日期:2013-08-20
  • 接受日期:2013-08-27
  • 在线发布日期: 2014-04-23
  • 出版日期: 2014-04-20