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中国慢性淋巴细胞白血病患者异常的 microRNA 表达。

Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia.

机构信息

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, China.

出版信息

Leuk Res. 2011 Jun;35(6):730-4. doi: 10.1016/j.leukres.2010.11.005. Epub 2010 Dec 3.

Abstract

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.

摘要

微小 RNA(miRNAs)是一类小的内源性 RNA,通过靶向 mRNA 的切割或翻译抑制来发挥重要的调节作用。许多报道表明,miRNAs 在恶性肿瘤和白血病的进展中起着关键作用。然而,中国慢性淋巴细胞白血病(CLL)患者的 miRNA 表达水平及其预后价值仍不清楚。我们在 CLL 单个核细胞中鉴定到 miR-15a、miR-16-1、miR-29b、miR-181a 和 miR-181b 不同程度的下调。此外,我们还发现 miR-29b 和 miR-181a/b 的表达与 IGHV 突变状态显著相关。还确定了预测靶基因 BCL-2 和 TCL-1 的转录本水平,与正常对照相比,CLL 患者的表达水平显著上调(P<0.001)。TCL-1 的高表达与侵袭性疾病特征显著相关。此外,在我们检查的 CLL 样本中,miRNAs(miR-16-1、miR-181a、miR-181b)与 BCL-2 水平之间存在负相关;此外,miRNAs(miR-16-1、miR-181a、miR-181b)与 TCL-1 之间也存在负相关,这表明这些 miRNAs 可能在转录水平上负调控靶 mRNA。这些不同的 miRNAs 可能在 CLL 的发病机制中发挥重要作用,并可能应用于 CLL 患者的预后评估。

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