文章：

小核仁和小Cajal体特异性RNA的表达模式是多发性骨髓瘤不同分子亚型的特征

The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

原文发布日期：2012-11-23

DOI: 10.1038/bcj.2012.41

类型: Original Article

开放获取: 是

英文摘要：

Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias.

摘要翻译： 

小核仁RNA（snoRNAs）与卡哈尔体特异性小RNA（scaRNAs）作为非编码RNA分子，通常位于宿主基因的内含子区域，参与其他RNA分子的成熟过程。近期研究发现，sno/scaRNAs表达水平的改变在癌症中可能具有病理学意义。本研究通过分析55例多发性骨髓瘤（MM）、8例继发性浆细胞白血病（sPCL）及4例正常对照中纯化的恶性浆细胞，系统阐明了MM中sno/scaRNAs的表达模式。结果显示，与正常浆细胞相比，MM尤其是sPCL存在整体性的sno/scaRNAs表达下调。在易位/细胞周期蛋白D4（TC4）型MM中，SCARNA22是唯一特征性表达的sno/scaRNA分子；而TC2组则呈现独特的sno/scaRNA表达谱，其位于15q11印记中心精细调控区域的SNORD115和SNORD116家族成员显著过表达，但该区域在MM中整体呈现低甲基化状态，且与SNORD115和SNORD116的表达水平无关。最后，通过整合基因表达谱和全基因组数据，我们揭示了sno/scaRNAs与宿主基因之间存在显著共表达现象，并发现等位基因失衡可能对特定snoRNAs的表达产生潜在影响。本研究拓展了当前对癌症中sno/scaRNAs失调机制的认识，为浆细胞恶性增殖疾病的生物分子复杂性提供了新依据。

原文链接：

The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma