Genome-wide analysis of small RNA and novel MicroRNA discovery in human acute lymphoblastic leukemia based on extensive sequencing approach.

Genome-wide analysis of small RNA and novel MicroRNA discovery in human acute lymphoblastic leukemia based on extensive sequencing approach.
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DOI:
10.1371/journal.pone.0006849
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发表时间:
2009-09-02
期刊:
影响因子:
3.7
通讯作者:
Chen YQ
Chen YQ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang H;Yang JH;Zheng YS;Zhang P;Chen X;Wu J;Xu L;Luo XQ;Ke ZY;Zhou H;Qu LH;Chen YQ

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MicroRNA (miRNA) 已被证明在各种细胞过程中发挥重要作用,并在包括白血病在内的癌症中充当肿瘤抑制因子或癌基因。大量新型 miRNA 和其他小调控 RNA 的鉴定将为了解它们在肿瘤发生中的作用提供有价值的见解。为了进一步了解与急性淋巴细胞白血病 (ALL) 相关的 miRNA 的作用,我们采用合成测序 (SBS) 策略对从 ALL 患者和正常供体制备的小 RNA 文库进行测序。我们总共从两个文库中鉴定出了 159 个新 miRNA 和 116 个新 miRNA*。在 159 个新的 miRNA 中,有 42 个在我们的数据集中被高度严格地鉴定出来。此外,我们证明了 ALL 患者和正常供体之间 20 个新识别的 miRNA 和几个已知的 miRNA 的不同表达模式,表明这些 miRNA 可能与 ALL 相关,并且可能构成 ALL 特异性 miRNA 特征。有趣的是,GO“生物过程”分类揭示了一组显着异常表达的 miRNA 与疾病复发相关,这意味着这些失调的 miRNA 可能通过调节参与疾病发展途径的基因来促进 ALL 的进展。该研究全面展示了人类急性淋巴细胞白血病中小 RNA 的表达情况,并重点介绍了 ALL 患者和正常供体之间差异表达的新型和已知 miRNA。据我们所知,这是第一项研究人类急性淋巴细胞白血病中全基因组已知的新型 miRNA 表达模式的研究。我们的数据显示,这些失调的 miRNA 可能与 ALL 或复发的发生有关。
MicroRNAs (miRNAs) have been proved to play an important role in various cellular processes and function as tumor suppressors or oncogenes in cancers including leukemia. The identification of a large number of novel miRNAs and other small regulatory RNAs will provide valuable insights into the roles they play in tumorgenesis. To gain further understanding of the role of miRNAs relevant to acute lymphoblastic leukemia (ALL), we employed the sequencing-by-synthesis (SBS) strategy to sequence small RNA libraries prepared from ALL patients and normal donors. In total we identified 159 novel miRNAs and 116 novel miRNA*s from both libraries. Among the 159 novel miRNAs, 42 were identified with high stringency in our data set. Furthermore, we demonstrated the different expression patterns of 20 newly identified and several known miRNAs between ALL patients and normal donors, suggesting these miRNAs may be associated with ALL and could constitute an ALL-specific miRNA signature. Interestingly, GO “biological process” classifications revealed that a set of significantly abnormally expressed miRNAs are associated with disease relapse, which implies that these dysregulated miRNAs might promote the progression of ALL by regulating genes involved in the pathway of the disease development. The study presents a comprehensive picture of the expression of small RNAs in human acute lymphoblastic leukemia and highlights novel and known miRNAs differentially expressed between ALL patients and normal donors. To our knowledge, this is the first study to look at genome-wide known and novel miRNA expression patterns in in human acute lymphoblastic leukemia. Our data revealed that these deregulated miRNAs may be associated with ALL or the onset of relapse.
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期刊: CELL
影响因子: 64.5
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