CircRNAs Dysregulated in Juvenile Myelomonocytic Leukemia: CircMCTP1 Stands Out
| Autor: | Anna Dal Molin, Mattias Hofmans, Enrico Gaffo, Alessia Buratin, Hélène Cavé, Christian Flotho, Valerie de Haas, Charlotte M. Niemeyer, Jan Stary, Pieter Van Vlierberghe, Jan Philippé, Barbara De Moerloose, Geertruij te Kronnie, Silvia Bresolin, Tim Lammens, Stefania Bortoluzzi |
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| Rok vydání: | 2020 |
| Předmět: |
EXPRESSION
0301 basic medicine RNA-Seq Computational biology Biology law.invention Cell and Developmental Biology 03 medical and health sciences regulatory networks 0302 clinical medicine law Circular RNA Gene expression microRNA Medicine and Health Sciences RAS PATHWAY medicine lcsh:QH301-705.5 Gene Myeloproliferative neoplasm CIRCULAR RNA Original Research Juvenile myelomonocytic leukemia MUTATIONS PROLIFERATION Cell Biology medicine.disease juvenile myelomonocytic leukemia APOPTOSIS microRNAs 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis Suppressor CELL-GROWTH COMPLEXES OVEREXPRESSION TRANSLATION CircRNAs Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Frontiers in Cell and Developmental Biology, Vol 8 (2021) |
| ISSN: | 2296-634X |
| Popis: | Juvenile myelomonocytic leukemia (JMML), a rare myelodysplastic/myeloproliferative neoplasm of early childhood, is characterized by clonal growth of RAS signaling addicted stem cells. JMML subtypes are defined by specific RAS pathway mutations and display distinct gene, microRNA (miRNA) and long non-coding RNA expression profiles. Here we zoom in on circular RNAs (circRNAs), molecules that, when abnormally expressed, may participate in malignant deviation of cellular processes. CirComPara software was used to annotate and quantify circRNAs in RNA-seq data of a “discovery cohort” comprising 19 JMML patients and 3 healthy donors (HD). In an independent set of 12 JMML patients and 6 HD, expression of 27 circRNAs was analyzed by qRT-PCR. CircRNA-miRNA-gene networks were reconstructed using circRNA function prediction and gene expression data. We identified 119 circRNAs dysregulated in JMML and 59 genes showing an imbalance of the circular and linear products. Our data indicated also circRNA expression differences among molecular subgroups of JMML. Validation of a set of deregulated circRNAs in an independent cohort of JMML patients confirmed the down-regulation of circOXNAD1 and circATM, and a marked up-regulation of circLYN, circAFF2, and circMCTP1. A new finding in JMML links up-regulated circMCTP1 with known tumor suppressor miRNAs. This and other predicted interactions with miRNAs connect dysregulated circRNAs to regulatory networks. In conclusion, this study provides insight into the circRNAome of JMML and paves the path to elucidate new molecular disease mechanisms putting forward circMCTP1 up-regulation as a robust example. |
| Databáze: | OpenAIRE |
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