Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Hematology, Fondazione Cà Granda IRCCS Policlinico, Milan, Italy.
Sci Rep. 2018 Apr 26;8(1):6557. doi: 10.1038/s41598-018-24701-8.
Multiple myeloma (MM) is a clonal proliferation of bone marrow plasma cells characterized by highly heterogeneous genetic background and clinical course, whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis and tumor evolution. Although still in its infancy, the role of lncRNAs in MM is progressively expanding. Besides studies on selected candidates, lncRNAs expression at genome-wide transcriptome level is confined to microarray technologies, thus investigating a limited collection of transcripts. In the present study investigating a cohort of 30 MM patients, a deep RNA-sequencing analysis overwhelmed previous array studies and allowed the most accurate definition of lncRNA transcripts structure and expression, ultimately providing a comprehensive catalogue of lncRNAs specifically associated with the main MM molecular subgroups and genetic alterations. Despite the small number of analyzed samples, the high accuracy of RNA-sequencing approach for complex transcriptome processing led to the identification of 391 deregulated lncRNAs, 67% of which were also detectable and validated by whole-transcript microarrays. In addition, we identified a list of lncRNAs, with potential relevance in MM, co-expressed and in close proximity to genes that might undergo a cis-regulatory relationship.
多发性骨髓瘤（MM）是骨髓浆细胞的克隆性增殖，其特征是遗传背景和临床病程高度异质性，其发病机制在很大程度上仍不清楚。长链非编码 RNA（lncRNAs）是一大类非蛋白编码 RNA，参与许多生理细胞和基因组过程以及致癌和肿瘤进化。尽管仍处于起步阶段，但 lncRNAs 在 MM 中的作用正在不断扩大。除了对选定候选者的研究外，lncRNAs 在全基因组转录组水平的表达仅限于微阵列技术，因此仅研究了有限的转录本。在本研究中，对 30 例 MM 患者进行了研究，深度 RNA 测序分析超越了以前的阵列研究，能够最准确地定义 lncRNA 转录本的结构和表达，最终提供了与 MM 主要分子亚群和遗传改变特异性相关的 lncRNAs 的综合目录。尽管分析的样本数量较少，但 RNA 测序方法对复杂转录组处理的高精度导致鉴定出 391 个失调的 lncRNAs，其中 67%也可以通过全转录微阵列检测和验证。此外，我们确定了一系列与 MM 具有潜在相关性的 lncRNAs，这些 lncRNAs 与可能发生顺式调控关系的基因共表达且紧密相邻。
