Waldenstrom巨球蛋白血症肿瘤细胞中的MicroRNA表达反映了正常和恶性细胞中的MicroRNA表达
MicroRNA expression in tumor cells from Waldenstrom's macroglobulinemia reflects both their normal and malignant cell counterparts
原文发布日期:2011-06-17
DOI: 10.1038/bcj.2011.25
类型: Original Article
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MicroRNAs (miRNAs) are involved in the regulation of many cellular processes including hematopoiesis, with the aberrant expression of differentiation-stage specific miRNA associated with lymphomagenesis. miRNA profiling has been essential for understanding the underlying biology of many hematological malignancies; however the miRNA signature of the diverse tumor clone associated with Waldenstrom's macroglobulinemia (WM), consisting of B lymphocytes, plasmacytes and lymphoplasmacytic cells, has not been characterized. We have investigated the expression of over 13 000 known and candidate miRNAs in both CD19+ and CD138+ WM tumor cells, as well as in their malignant and non-malignant counterparts. Although neither CD19+ nor CD138+ WM cells were defined by a distinct miRNA profile, the combination of all WM cells revealed a unique miRNA transcriptome characterized by the dysregulation of many miRNAs previously identified as crucial for normal B-cell lineage differentiation. Specifically, miRNA-9*/152/182 were underexpressed in WM, whereas the expression of miRNA-21/125b/181a/193b/223/363 were notably increased (analysis of variance; P<0.0001). Future studies focusing on the effects of these dysregulated miRNAs will provide further insight into the mechanisms responsible for the pathogenesis of WM.
MicroRNAs(miRNAs)参与调控包括造血作用在内的多种细胞过程,其分化阶段特异性miRNA的异常表达与淋巴瘤发生相关。miRNA谱分析对理解许多血液系统恶性肿瘤的潜在生物学机制至关重要;然而,与华氏巨球蛋白血症(WM)相关的由B淋巴细胞、浆细胞和淋巴浆细胞组成的多样化肿瘤克隆的miRNA特征尚未明确。我们研究了CD19+和CD138+ WM肿瘤细胞及其恶性与非恶性对应细胞中13,000多个已知候选miRNA的表达。尽管CD19+和CD138+ WM细胞均未呈现独特的miRNA谱,但所有WM细胞的组合揭示了一个独特的miRNA转录组特征,其特征表现为许多先前被确认为正常B细胞谱系分化关键的miRNAs出现失调。具体而言,miRNA-9*/152/182在WM中表达下调,而miRNA-21/125b/181a/193b/223/363的表达显著增加(方差分析;P<0.0001)。未来针对这些失调miRNAs效应的研究将为进一步理解WM发病机制提供更多见解。
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