Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia

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.

微小RNA（miRNAs）是一类内源性小RNA，它们通过靶向信使RNA进行切割或翻译抑制来发挥重要的调控作用。许多报道表明，miRNAs在恶性肿瘤以及白血病的进展调控中起着关键作用。然而，中国慢性淋巴细胞白血病（CLL）患者中miRNAs的表达水平及其预后价值仍不明确。我们发现CLL单核细胞中miR - 15a、miR - 16 - 1、miR - 29b、miR - 181a和miR - 181b存在不同程度的下调。此外，我们还发现miR - 29b和miR - 181a/b的表达与免疫球蛋白重链可变区（IGHV）突变状态显著相关。我们还测定了预测的靶基因BCL - 2和TCL - 1的转录水平，与正常对照相比，CLL患者中这些基因的表达水平显著上调（P < 0.001）。TCL - 1的高表达与疾病的侵袭性特征显著相关。此外，在我们检测的CLL样本中，观察到miRNAs（miR - 16 - 1、miR - 181a、miR - 181b）与BCL - 2水平呈负相关；并且miRNAs（miR - 16 - 1、miR - 181a、miR - 181b）与TCL - 1之间也呈负相关，这表明这些miRNAs可能在转录水平上对靶信使RNA进行负调控。这些不同的miRNAs可能在CLL的发病机制中起重要作用，并可能用于CLL患者的预后评估。（C）2010爱思唯尔有限公司。保留所有权利。