期刊
LEUKEMIA
卷 35, 期 5, 页码 1438-1450出版社
SPRINGERNATURE
DOI: 10.1038/s41375-021-01147-y
关键词
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资金
- Instituto de Salud Carlos III (ISCIII) [PI14/01867, PI16/02024, PI17/00701, PI19/01352]
- Fundacio La Marato de TV3
- Cancer Research UK [C355/A26819]
- FC AECC
- AIRC
- CIBERONC [CB16/12/00489, CB16/12/00225]
- FEDER funds
- MINECO Explora (RTHALMY)
- Gobierno de Navarra
- Departamento de Salud [40/2016]
- Departamento de Industria (Proyecto Estrategico, Reto Genomica, DIANA)
- Fundacion Ramon Areces (PREMAMM)
- Paula and Rodger Riney Foundation
- European Union's Seventh Framework Programme through the Blueprint Consortium [282510]
- Generalitat de Catalunya Suport Grups de Recerca [AGAUR 2017-SGR-736]
- Multiple Myeloma Research Foundation Networks of excellence
- International Myeloma Foundation (Brian van Novis)
- Qatar National Research Fund [7-916-3-237]
- PFIS from Instituto de Salud Carlos III (ISCIII) [FI16/00275, FI17/00297]
- Gilead Research Scholar in Hematology/Oncology award
- FPU Fellowship of the Spanish Government
- AOI grant of the Spanish Association Against Cancer
- Chemotherapy Foundation
- NIH-NCI [R01 CA187109]
- TRANSCAN (EPICA)
- TRANSCAN (Immunocell)
In this study, researchers identified a large number of novel lncRNAs in MM, which showed more heterogeneous expression compared to coding genes, and were associated with the biological and clinical behavior of the disease. Through the study of lncRNAs, potential biomarkers related to MM progression and survival rates were discovered.
Multiple myeloma (MM) is an incurable disease, whose clinical heterogeneity makes its management challenging, highlighting the need for biological features to guide improved therapies. Deregulation of specific long non-coding RNAs (lncRNAs) has been shown in MM, nevertheless, the complete lncRNA transcriptome has not yet been elucidated. In this work, we identified 40,511 novel lncRNAs in MM samples. lncRNAs accounted for 82% of the MM transcriptome and were more heterogeneously expressed than coding genes. A total of 10,351 overexpressed and 9,535 downregulated lncRNAs were identified in MM patients when compared with normal bone-marrow plasma cells. Transcriptional dynamics study of lncRNAs in the context of normal B-cell maturation revealed 989 lncRNAs with exclusive expression in MM, among which 89 showed de novo epigenomic activation. Knockdown studies on one of these lncRNAs, SMILO (specific myeloma intergenic long non-coding RNA), resulted in reduced proliferation and induction of apoptosis of MM cells, and activation of the interferon pathway. We also showed that the expression of lncRNAs, together with clinical and genetic risk alterations, stratified MM patients into several progression-free survival and overall survival groups. In summary, our global analysis of the lncRNAs transcriptome reveals the presence of specific lncRNAs associated with the biological and clinical behavior of the disease.
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