Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs
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DOI:
10.1182/blood-2010-05-285403
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发表时间:
2010-12-02
期刊:
影响因子:
20.3
通讯作者:
Dave, Sandeep S.
Dave, Sandeep S.
中科院分区:
医学1区
文献类型:
--
作者:
Jima, Dereje D.;Zhang, Jenny;Dave, Sandeep S.

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到目前为止,微rna (miRNA)在几乎所有的生物系统中都有作用。在完整描述它们的作用之前,必须先鉴定任何系统中存在的所有mirna。我们通过对31个包括B细胞分化谱和常见恶性表型的正常和恶性B细胞样本进行深度测序,阐明了正常和恶性B细胞的完整小RNA转录组。我们鉴定了333个已知的mirna的表达,这是之前在任何组织类型中识别的数量的两倍多。我们进一步在正常和恶性B细胞中鉴定了286个候选新型mirna的表达。使用定量聚合酶链反应,这些mirna的验证率很高(92%),并且我们证明了它们在区分淋巴瘤临床相关亚群中的应用。我们进一步证明了一个新的miRNA集群,先前被注释为假设的基因LOC100130622,包含6个调节转化生长因子- β途径的新型miRNA。因此,我们的工作表明,目前大多数细胞类型中存在的超过三分之一的mirna是未知的,这些mirna可能调节重要的细胞功能。(血。2010;116 (23):e118-e127)
A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-beta pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. (Blood. 2010;116(23):e118-e127)