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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AG02
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High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AG02

机译：高危骨髓瘤与miRNA的整体升高和EIF2C2 / AG02的过度表达有关

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摘要

MicroRNAs (miRNAs) are noncoding RNAs that regulate global gene expression. miRNAs often act synergistically to repress target genes, and their dysregulation can contribute to the initiation and progression of a variety of cancers. The clinical relationship between global expression of miRNA and mRNA in cancer has not been studied in detail. We used whole-genome microarray analyses of CD138-enriched plasma cells from 52 newly diagnosed cases of multiple myeloma to correlate miRNA expression profiles with a validated mRNA-based risk stratification score, proliferation index, and predefined gene sets. In stark contrast to mRNAs, we discovered that all tested miRNAs were significantly up-regulated in high-risk disease as defined by a validated 70-gene risk score (P < 0.01) and proliferation index (P < 0.05). Increased expression of EIF2C2/AGO2, a master regulator of the maturation and function of miRNAs and a component of the 70-gene mRNA risk model, is driven by DNA copy number gains in MM. Silencing of AGO2 dramatically decreased viability in MM cell lines. Genome-wide elevated expression of miRNAs in high-risk MM may be secondary to deregulation of AGO2 and the enzyme complexes that regulate miRNA maturation and function.
机译：微小RNA（miRNA）是调节全局基因表达的非编码RNA。 miRNA通常协同作用来抑制靶基因，它们的失调可导致多种癌症的发生和发展。尚未详细研究癌症中miRNA和mRNA的整体表达之间的临床关系。我们使用来自52个新诊断的多发性骨髓瘤病例的富含CD138的浆细胞的全基因组微阵列分析，将miRNA表达谱与经过验证的基于mRNA的风险分层评分，增殖指数和预定的基因组相关联。与mRNA形成鲜明对比的是，我们发现，经验证的70个基因的风险评分（P <0.01）和增殖指数（P <0.05）定义，所有测试的miRNA在高危疾病中均显着上调。 EIF2C2 / AGO2表达的增加是MM中DNA拷贝数的增加，而EIF2C2 / AGO2是miRNA的成熟和功能的主要调节者，也是70基因mRNA风险模型的组成部分，其表达增加。 AGO2的沉默大大降低了MM细胞系的生存能力。全基因组高风险MM中miRNA的表达升高可能是AGO2和调节miRNA成熟和功能的酶复合物失调的继发因素。

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  • 来源
  • 作者

    Yiming Zhou; Lijuan Chen; Bart Barlogie; Owen Stephens; Xiaosong Wu; David R. Williams; Marie-Astrid Cartron; Frits van Rhee; Bijay Nair; Sarah Waheed; Mauricio Pineda-Roman; Yazan Alsayed; Elias Anaissie; John D. Shaughnessy Jr.;

  • 作者单位

    Donna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205 Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029,China;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

    rnDonna D. and Donald M. Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    DICER1; expression profile; multiple myeloma; risk stratification; system biology;

    机译：DICER1;表达谱;多发性骨髓瘤;风险分层;系统生物学;

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