文章：

慢性淋巴细胞白血病（CLL）中失调miRNA的RNA-Seq谱分析及其对临床结局的影响

RNA-Seq profiling of deregulated miRs in CLL and their impact on clinical outcome

原文发布日期：2020-01-13

DOI: 10.1038/s41408-019-0272-y

类型: Article

开放获取: 是

英文摘要：

Abnormal expression patterns of regulatory small non-coding RNA (sncRNA) molecules such as microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) play an important role in the development and progression of cancer. Identification of clinically relevant sncRNA signatures could, therefore, be of tremendous translational value. In the present study, genome-wide small RNA sequencing identified a unique pattern of differential regulation of eight miRs in Chronic Lymphocytic Leukemia (CLL). Among these, three were up-regulated (miR-1295a, miR-155, miR-4524a) and five were down-regulated (miR-30a, miR-423, miR-486*, let-7e, and miR-744) in CLL. Altered expression of all these eight differentially expressed miRs (DEMs) was validated by RQ-PCR. Besides, seven novel sequences identified to have elevated expression levels in CLL turned out to be transfer RNA (tRNA)/piRNAs (piRNA-30799, piRNA-36225)/snoRNA (SNORD43) related. Multivariate analysis showed that miR-4524a (HR: 1.916, 95% CI: 1.080–3.4, p value: 0.026) and miR-744 (HR: 0.415, 95% CI: 0.224–0.769, p value: 0.005) were significantly associated with risk and time to first treatment. Further investigations could help establish the scope of integration of these DEM markers into risk stratification designs and prognostication approaches for CLL.
 

摘要翻译： 

调控性小非编码RNA（sncRNA）分子如微小RNA（miR）、piwi相互作用RNA（piRNA）及小核仁RNA（snoRNA）的异常表达模式在癌症发生发展中具有重要作用。因此，鉴定临床相关的sncRNA特征具有重大转化价值。本研究通过全基因组小RNA测序，发现慢性淋巴细胞白血病（CLL）中八种miR存在独特的差异调控模式：其中三种表达上调（miR-1295a、miR-155、miR-4524a），五种表达下调（miR-30a、miR-423、miR-486*、let-7e和miR-744）。通过RQ-PCR验证了这八种差异表达miR（DEM）的表达改变。此外，在CLL中表达升高的七个新序列被证实与转移RNA（tRNA）/piRNA（piRNA-30799、piRNA-36225）/snoRNA（SNORD43）相关。多变量分析显示miR-4524a（风险比：1.916，95%置信区间：1.080-3.4，p值：0.026）和miR-744（风险比：0.415，95%置信区间：0.224-0.769，p值：0.005）与首次治疗风险和治疗时间显著相关。进一步研究有助于将这些DEM标志物整合至CLL风险分层设计和预后评估体系。

原文链接：

RNA-Seq profiling of deregulated miRs in CLL and their impact on clinical outcome