Gassner Franz J, Zaborsky Nadja, Feldbacher Daniel, Greil Richard, Geisberger Roland
Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Paracelsus Medical University, Cancer Cluster Salzburg, Müllner Hauptstrasse 48, 5020 Salzburg, Austria.
Department of Biosciences, University of Salzburg, Hellbrunner Strasse, 34, 5020 Salzburg, Austria.
Cancers (Basel). 2020 May 5;12(5):1159. doi: 10.3390/cancers12051159.
Chronic lymphocytic leukemia (CLL) is a high incidence B cell leukemia with a highly variable clinical course, leading to survival times ranging from months to several decades. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression levels of genes by binding to the untranslated regions of transcripts. Although miRNAs have been previously shown to play a crucial role in CLL development, progression and treatment resistance, their further processing and diversification by RNA editing (specifically adenosine to inosine or cytosine to uracil deamination) has not been addressed so far. In this study, we analyzed next generation sequencing data to provide a detailed map of adenosine to inosine and cytosine to uracil changes in miRNAs from CLL and normal B cells. Our results reveal that in addition to a CLL-specific expression pattern, there is also specific RNA editing of many miRNAs, particularly miR-3157 and miR-6503, in CLL. Our data draw further light on how miRNAs and miRNA editing might be implicated in the pathogenesis of the disease.
慢性淋巴细胞白血病(CLL)是一种发病率较高的B细胞白血病,其临床病程高度可变,生存期从数月到数十年不等。微小RNA(miRNA)是一类小的非编码RNA,通过与转录本的非翻译区结合来调节基因的表达水平。尽管此前已表明miRNA在CLL的发生、发展和治疗耐药中起关键作用,但迄今为止,它们通过RNA编辑(特别是腺苷到次黄嘌呤或胞嘧啶到尿嘧啶的脱氨基作用)的进一步加工和多样化尚未得到研究。在本研究中,我们分析了二代测序数据,以提供CLL和正常B细胞中miRNA腺苷到次黄嘌呤以及胞嘧啶到尿嘧啶变化的详细图谱。我们的结果表明,除了CLL特异性表达模式外,CLL中许多miRNA,特别是miR-3157和miR-6503,还存在特异性RNA编辑。我们的数据进一步揭示了miRNA和miRNA编辑可能如何参与该疾病的发病机制。