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

The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma.
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DOI:
10.1038/bcj.2012.41
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发表时间:
2012-11-23
影响因子:
12.8
通讯作者:
Neri, A.
Neri, A.
中科院分区:
医学1区
文献类型:
--
作者:
Ronchetti, D.;Todoerti, K.;Tuana, G.;Agnelli, L.;Mosca, L.;Lionetti, M.;Fabris, S.;Colapietro, P.;Miozzo, M.;Ferrarini, M.;Tassone, P.;Neri, A.

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小核仁RNA(SnoRNAs)和小Cajal体特异性RNAs(ScaRNAs)是参与其他RNA分子成熟的非编码RNA,通常位于宿主基因的内含子中。现在发现,sno/scaRNAs表达改变可能在癌症中起到病理作用。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例正常对照的纯化恶性浆细胞的分析,阐明了sNO/scaRNAs在多发性骨髓瘤(MM)中的表达模式。总体而言,与正常浆细胞相比,在MMS中发现了sNO/scaRNAs的全球下调,在sPCL中更是如此。SCARNA22是唯一具有易位/细胞周期蛋白D4(TC4)MM特征的sNO/Scarna,而TC2组表现出明显的sNO/Scarna特征,SNORD115和SNORD116家族的成员位于15q11的印记中心精细调控的区域,然而,这导致MMS的总体低甲基化独立于SNORD115和SNORD116的表达水平。最后,结合可获得的基因表达和全基因组数据的综合分析揭示了显著的sno/scaRNAs/宿主基因的共表达,以及等位基因失衡对特定snoRNAs表达的可能影响。我们的数据扩展了目前癌症中sNO/scaRNAs去调控的观点,并为浆细胞癌的生物分子复杂性增加了新的信息。
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.
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