文章：

通过小RNA深度测序扩展多发性骨髓瘤中表达的miRNA和miRNA偏移RNA的种类

Expanding the repertoire of miRNAs and miRNA-offset RNAs expressed in multiple myeloma by small RNA deep sequencing

原文发布日期：2019-02-19

DOI: 10.1038/s41408-019-0184-x

类型: Article

开放获取: 是

英文摘要：

Microarray analysis of the multiple myeloma (MM) miRNome has unraveled the differential expression of miRNAs in cytogenetic subgroups, their involvement in the tumor biology and their effectiveness in prognostic models. Herein, the small RNA transcriptional landscape in MM has been investigated exploiting the possibilities offered by small RNA-seq, including accurate quantification of known mature species, discovery and characterization of isomiRs, and miRNA-offset RNAs (moRNAs). Matched small RNA-seq and miRNA GeneChip® microarray expression profiles were obtained in a representative panel of 30 primary MM tumors, fully characterized for genomic aberrations and mutations. RNA-seq and microarray gave concordant estimations of known species. Enhanced analysis of RNA-seq data with the miR&moRe pipeline led to the characterization of 655 known and 17 new mature miRNAs and of 74 moRNAs expressed in the considered cohort, 5 of which (moR-150-3p, moR-24-2-5p, moR-421-5p, moR-21-5p, and moR-6724-5p) at high level. Ectopic expression of miR-135a-3p in t(4;14) patients, upregulation of moR-150-3p and moR-21-5p in t(14;16)/t(14;20) samples, and of moR-6724-1-5p in patients overexpressing CCND1 were uncovered and validated by qRT-PCR. Overall, RNA-seq offered a more complete overview of small non-coding RNA in MM tumors, indicating specific moRNAs that demand further investigations to explore their role in MM biology.

摘要翻译： 

多发性骨髓瘤（MM）miRNA组的微阵列分析揭示了miRNA在细胞遗传学亚组中的差异表达、它们在肿瘤生物学中的参与以及它们在预后模型中的有效性。在此，利用小RNA测序提供的可能性，研究了MM中小RNA的转录景观，包括已知成熟物种的准确量化、isomiRs的发现和表征，以及miRNA偏移RNA（moRNAs）。在一个代表性的30个原发性MM肿瘤样本中，获得了匹配的小RNA测序和miRNA GeneChip®微阵列表达谱，这些样本已完全表征了基因组畸变和突变。RNA测序和微阵列对已知物种的估计结果一致。使用miR&moRe流程对RNA测序数据进行增强分析，表征了655个已知和17个新的成熟miRNA，以及在该队列中表达的74个moRNA，其中5个（moR-150-3p、moR-24-2-5p、moR-421-5p、moR-21-5p和moR-6724-5p）表达水平较高。在t(4;14)患者中发现了miR-135a-3p的异位表达，在t(14;16)/t(14;20)样本中moR-150-3p和moR-21-5p的上调，以及在过表达CCND1的患者中moR-6724-1-5p的上调，这些结果通过qRT-PCR进行了验证。总体而言，RNA测序提供了MM肿瘤中小非编码RNA的更完整概述，指出了需要进一步研究以探索其在MM生物学中作用的特定moRNA。

原文链接：

Expanding the repertoire of miRNAs and miRNA-offset RNAs expressed in multiple myeloma by small RNA deep sequencing