Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia

Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia
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中国慢性淋巴细胞白血病患者的异常microRNA表达

DOI:
10.1016/j.leukres.2010.11.005
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发表时间:
2011-06-01
期刊:
影响因子:
2.7
通讯作者:
Li, Jian-Yong
Li, Jian-Yong
中科院分区:
医学3区
文献类型:
--
作者:
Zhu, Dan-Xia;Miao, Kou-Rong;Li, Jian-Yong

文献摘要

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微小RNA(microRNAs,miRNAs)是一类内源性小RNA,通过靶向mRNA进行切割或翻译抑制而发挥重要的调控作用。许多研究表明,miRNAs在恶性肿瘤中起着重要作用,并在白血病的发生发展中起着重要的调节作用。然而,miRNAs在中国慢性淋巴细胞白血病(CLL)患者中的表达水平及其预后价值尚不清楚。我们鉴定了miR-15 a、miR-16-1、miR-29 b、miR-181 a和miR-181 b在CLL单核细胞中不同程度的下调。此外,我们已经鉴定了miR-29 B和miR-181 a/B表达与IGHV突变状态显著相关。同时检测预测靶基因BCL-2和TCL-1的转录水平,CLL患者的表达水平明显高于正常对照组(P < 0.001)。TCL-1的高表达与侵袭性疾病特征显著相关。此外,在我们检测的CLL样本中,miR-16-1、miR-181 a、miR-181 b与BCL-2水平呈负相关; miR-16-1、miR-181 a、miR-181 b与TCL-1水平呈负相关,提示这些miRNA可能在转录水平负调控靶mRNA。这些不同的miRNAs可能在CLL的发病机制中发挥重要作用,并可能用于评估CLL患者的预后。(C)2010爱思唯尔有限公司保留所有权利。
MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. Many reports have indicated that miRNAs play a critical role in malignancies, and regulations in the progression of leukemia. However, the miRNAs expression level in Chinese patients with chronic lymphocytic leukemia (CLL), and its prognostic value remain elusive. We identified various degrees of down-regulation of miR-15a, miR-16-1, miR-29b, miR-181a and miR-181b in CLL mononuclear cells. Moreover, we have identified miR-29b and miR-181a/b expression significantly correlated with IGHV mutational status. Transcript levels of predicted target genes BCL-2 and TCL-1 were also determined, and the expression levels were significantly upregulated in CLL patients compared with normal controls (P < 0.001). Higher expression of TCL-1 was significantly correlated with aggressive disease features. In addition, an inverse correlation was observed in the CLL samples we examined between miRNAs (miR-16-1, miR-181a, miR-181b) and BCL-2 level; furthermore, an inverse correlation was also observed between miRNAs (miR-16-1, miR-181a, miR-181b) and TCL-1, which suggest that these miRNAs may implicate in negatively regulating target mRNA at transcriptional level. These different miRNAs may play an important role in the pathogenesis of CLL and might be applied for the assessment of prognosis in patients with CLL. (C) 2010 Elsevier Ltd. All rights reserved.