Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma.
Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma.
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DOI：
10.1038/bcj.2013.49
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发表时间：
2013-10-11
影响因子：
12.8
通讯作者：
Lui, W-O
中科院分区：
文献类型：
--
作者：
Caramuta, S.;Lee, L.;Ozata, D. M.;Akcakaya, P.;Georgii-Hemming, P.;Xie, H.;Amini, R-M;Lawrie, C. H.;Enblad, G.;Larsson, C.;Berglund, M.;Lui, W-O
在弥漫性大B细胞淋巴瘤（DLBCL）中已经记录了microRNA（miRNA）表达的失调。然而，miRNA及其机制在DLBCL中的影响尚未完全确定。在这里，我们评估了miRNA表达及其加工基因在DLBCL发展中的作用。使用微阵列和RT-qPCR方法，我们定量了75个DLBCL（56个新生和19个转化）和10个淋巴结（LN）中的全局miRNA和miRNA加工基因表达的核心组分。在DLBCL和LN之间，或在从头和转化的DLBCL之间鉴定了差异miRNA特征。我们还鉴定了与生发中心B细胞表型、BCL 6和IRF 4表达以及临床分期相关的miRNA亚群。此外，我们发现与LN相比，新发DLBCL中TARBP 2显著过表达，与新发病例相比，转化病例中DROSHA、DICER、TARBP 2和PACT的表达降低。有趣的是，具有高TARBP 2和DROSHA表达的病例具有较差的化疗反应。我们进一步表明，TARBP 2可以调节DLBCL中的miRNA加工效率，并且其表达抑制会降低DLBCL细胞系中的细胞生长并增加细胞凋亡。我们的研究结果为理解DLBCL中的miRNAs及其机制提供了新的见解。
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.
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影响因子：
6.4
作者：
Chang, Steven S.;Jiang, Wei Wen;Smith, Ian;Poeta, Luana M.;Begum, Shahnaz;Glazer, Chad;Shan, Shannon;Westra, William;Sidransky, David;Califano, Joseph A.
通讯作者：
Califano, Joseph A.
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
6.5
作者：
Lawrie, Charles H.;Gal, Shira;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
影响因子：
7.5
作者：
Berglund, M;Enblad, G;Lagercrantz, S
通讯作者：
Lagercrantz, S
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM