Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy.
Blood Cancer J. 2012 Nov 23;2(11):e96. doi: 10.1038/bcj.2012.41.
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.
小核仁 RNA(snoRNAs)和小 Cajal 体特异性 RNA(scaRNAs)是非编码 RNA,参与其他 RNA 分子的成熟,通常位于宿主基因的内含子中。现在已经出现,改变 sno/scaRNAs 的表达可能在癌症中具有病理作用。本研究通过对 55 例多发性骨髓瘤(MM)、8 例继发性浆细胞白血病(sPCL)和 4 例正常对照中纯化的恶性浆细胞进行分析,阐明了 sno/scaRNAs 在多发性骨髓瘤中的表达模式。总的来说,与正常浆细胞相比,MM 和 sPCL 中 sno/scaRNAs 表达普遍下调。虽然 SCARNA22 是唯一特征性的 sno/scaRNA 转位/cyclin D4(TC4)MM,但 TC2 组显示出独特的 sno/scaRNA 特征,过度表达位于印迹中心精细调控的 15q11 区域的 SNORD115 和 SNORD116 家族成员,然而,在 MM 中,无论 SNORD115 和 SNORD116 的表达水平如何,总体上呈低甲基化。最后,与可用的基因表达和全基因组数据的综合分析揭示了 sno/scaRNAs/宿主基因的显著共表达,并推测等位基因失衡对特定 snoRNAs 表达的影响。我们的数据扩展了 sno/scaRNAs 在癌症中失调的现有观点,并为浆细胞发育异常的生物分子复杂性提供了新的信息。