Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, People's Republic of China.
PLoS One. 2009 Sep 2;4(9):e6849. doi: 10.1371/journal.pone.0006849.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSION/SIGNIFICANCE: 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.
MicroRNAs（miRNAs）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作为肿瘤抑制因子或癌基因发挥作用。大量新的miRNAs 和其他小调控 RNA 的鉴定将为它们在肿瘤发生中的作用提供有价值的见解。
方法/主要发现：为了更深入地了解与急性淋巴细胞白血病（ALL）相关的 miRNAs 的作用，我们采用测序合成（SBS）策略对来自 ALL 患者和正常供体的小 RNA 文库进行测序。总共从两个文库中鉴定出 159 个新的 miRNAs 和 116 个新的 miRNA*。在 159 个新的 miRNAs 中，有 42 个在我们的数据集中被严格鉴定出来。此外，我们证明了 20 个新鉴定的和几个已知的 miRNAs 在 ALL 患者和正常供体之间的不同表达模式，这表明这些 miRNAs 可能与 ALL 相关，并可能构成 ALL 特异性 miRNA 特征。有趣的是，GO“生物过程”分类显示，一组显著异常表达的 miRNAs 与疾病复发有关，这意味着这些失调的 miRNAs 可能通过调节参与疾病发展途径的基因来促进 ALL 的进展。
结论/意义：该研究全面描绘了人类急性淋巴细胞白血病中小 RNA 的表达情况，并突出了 ALL 患者和正常供体之间差异表达的新的和已知的 miRNAs。据我们所知，这是首次研究人类急性淋巴细胞白血病中全基因组已知和新的 miRNA 表达模式。我们的数据表明，这些失调的 miRNAs 可能与 ALL 或复发的发生有关。
