文章：

microRNA及其机制在弥漫性大B细胞淋巴瘤发病机制中的作用

Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma

原文发布日期：2013-10-11

DOI: 10.1038/bcj.2013.49

类型: Original Article

开放获取: 是

英文摘要：

Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL.

摘要翻译： 

microRNA（miRNA）表达的失调已在弥漫大B细胞淋巴瘤（DLBCL）中得到记录。然而，miRNA及其机制在DLBCL中的作用尚未完全明确。本研究评估了miRNA表达及其加工基因在DLBCL发展中的作用。通过微阵列和RT-qPCR技术，我们定量分析了75例DLBCL（56例为原发性和19例为转化型）和10个淋巴结（LN）中全局miRNA及miRNA加工基因核心组件的表达。研究发现了DLBCL与LN之间、以及原发性与转化型DLBCL之间的差异miRNA特征。我们还识别出与生发中心B细胞表型、BCL6和IRF4表达及临床分期相关的miRNA亚群。此外，与原发DLBCL相比，转化型病例中DROSHA、DICER、TARBP2和PACT表达下降。值得注意的是，高表达TARBP2和DROSHA的病例对化疗反应较差。我们进一步证明TARBP2可调控DLBCL中miRNA的加工效率，抑制其表达能降低DLBCL细胞系的细胞生长并增加凋亡。这些发现为理解miRNA及其机制在DLBCL中的作用提供了新见解。

原文链接：

Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma