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Large-scale circular RNA deregulation in T-ALL : unlocking unique ectopic expression of molecular subtypes

(2020) BLOOD ADVANCES. 4(23). p.5902-5914
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Abstract
Circular RNAs (circRNAs) are stable RNA molecules that can drive cancer through interactions with microRNAs and proteins and by the expression of circRNA encoded peptides. The aim of the study was to define the circRNA landscape and potential impact in T-cell acute lymphoblastic leukemia (T-ALL). Analysis by CirComPara of RNA-sequencing data from 25 T-ALL patients, immature, HOXA overexpressing, TLX1, TLX3, TAL1, or LMO2 rearranged, and from thymocyte populations of human healthy donors disclosed 68 554 circRNAs. Study of the top 3447 highly expressed circRNAs identified 944 circRNAs with significant differential expression between malignant T cells and normal counterparts, with most circRNAs displaying increased expression in T-ALL. Next, we defined subtype-specific circRNA signatures in molecular genetic subgroups of human T-ALL. In particular, circZNF609, circPSEN1, circKPNA5, and circCEP70 were upregulated in immature, circTASP1, circZBTB44, and circBACH1 in TLX3, circHACD1, and circSTAM in HOXA, circCAMSAP1 in TLX1, and circCASC15 in TAL-LMO. Backsplice sequences of 14 circRNAs ectopically expressed in T-ALL were confirmed, and overexpression of circRNAs in T-ALL with specific oncogenic lesions was substantiated by quantification in a panel of 13 human cell lines. An oncogenic role of circZNF609 in T-ALL was indicated by decreased cell viability upon silencing in vitro. Furthermore, functional predictions identified circRNA-microRNA gene axes informing modes of circRNA impact in molecular subtypes of human T-ALL.
Keywords
SIGNALING PATHWAY, SIGNATURES DEFINE, CELL, GENE, LEUKEMIA, PROGRESSION, ACTIVATION, CANCER, TRANSLATION, COMPLEXES

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MLA
Buratin, Alessia, et al. “Large-Scale Circular RNA Deregulation in T-ALL : Unlocking Unique Ectopic Expression of Molecular Subtypes.” BLOOD ADVANCES, vol. 4, no. 23, 2020, pp. 5902–14, doi:10.1182/bloodadvances.2020002337.
APA
Buratin, A., Paganin, M., Gaffo, E., Dal Molin, A., Roels, J., Germano, G., … Bortoluzzi, S. (2020). Large-scale circular RNA deregulation in T-ALL : unlocking unique ectopic expression of molecular subtypes. BLOOD ADVANCES, 4(23), 5902–5914. https://doi.org/10.1182/bloodadvances.2020002337
Chicago author-date
Buratin, Alessia, Maddalena Paganin, Enrico Gaffo, Anna Dal Molin, Juliette Roels, Giuseppe Germano, Maria Teresa Siddi, et al. 2020. “Large-Scale Circular RNA Deregulation in T-ALL : Unlocking Unique Ectopic Expression of Molecular Subtypes.” BLOOD ADVANCES 4 (23): 5902–14. https://doi.org/10.1182/bloodadvances.2020002337.
Chicago author-date (all authors)
Buratin, Alessia, Maddalena Paganin, Enrico Gaffo, Anna Dal Molin, Juliette Roels, Giuseppe Germano, Maria Teresa Siddi, Valentina Serafin, Matthias De Decker, Stéphanie Gachet, Kaat Durinck, Franki Speleman, Tom Taghon, Geertruij te Kronnie, Pieter Van Vlierberghe, and Stefania Bortoluzzi. 2020. “Large-Scale Circular RNA Deregulation in T-ALL : Unlocking Unique Ectopic Expression of Molecular Subtypes.” BLOOD ADVANCES 4 (23): 5902–5914. doi:10.1182/bloodadvances.2020002337.
Vancouver
1.
Buratin A, Paganin M, Gaffo E, Dal Molin A, Roels J, Germano G, et al. Large-scale circular RNA deregulation in T-ALL : unlocking unique ectopic expression of molecular subtypes. BLOOD ADVANCES. 2020;4(23):5902–14.
IEEE
[1]
A. Buratin et al., “Large-scale circular RNA deregulation in T-ALL : unlocking unique ectopic expression of molecular subtypes,” BLOOD ADVANCES, vol. 4, no. 23, pp. 5902–5914, 2020.
@article{8690979,
  abstract     = {{Circular RNAs (circRNAs) are stable RNA molecules that can drive cancer through interactions with microRNAs and proteins and by the expression of circRNA encoded peptides. The aim of the study was to define the circRNA landscape and potential impact in T-cell acute lymphoblastic leukemia (T-ALL). Analysis by CirComPara of RNA-sequencing data from 25 T-ALL patients, immature, HOXA overexpressing, TLX1, TLX3, TAL1, or LMO2 rearranged, and from thymocyte populations of human healthy donors disclosed 68 554 circRNAs. Study of the top 3447 highly expressed circRNAs identified 944 circRNAs with significant differential expression between malignant T cells and normal counterparts, with most circRNAs displaying increased expression in T-ALL. Next, we defined subtype-specific circRNA signatures in molecular genetic subgroups of human T-ALL. In particular, circZNF609, circPSEN1, circKPNA5, and circCEP70 were upregulated in immature, circTASP1, circZBTB44, and circBACH1 in TLX3, circHACD1, and circSTAM in HOXA, circCAMSAP1 in TLX1, and circCASC15 in TAL-LMO. Backsplice sequences of 14 circRNAs ectopically expressed in T-ALL were confirmed, and overexpression of circRNAs in T-ALL with specific oncogenic lesions was substantiated by quantification in a panel of 13 human cell lines. An oncogenic role of circZNF609 in T-ALL was indicated by decreased cell viability upon silencing in vitro. Furthermore, functional predictions identified circRNA-microRNA gene axes informing modes of circRNA impact in molecular subtypes of human T-ALL.}},
  author       = {{Buratin, Alessia and Paganin, Maddalena and Gaffo, Enrico and Dal Molin, Anna and Roels, Juliette and Germano, Giuseppe and Siddi, Maria Teresa and Serafin, Valentina and De Decker, Matthias and Gachet, Stéphanie and Durinck, Kaat and Speleman, Franki and Taghon, Tom and te Kronnie, Geertruij and Van Vlierberghe, Pieter and Bortoluzzi, Stefania}},
  issn         = {{2473-9529}},
  journal      = {{BLOOD ADVANCES}},
  keywords     = {{SIGNALING PATHWAY,SIGNATURES DEFINE,CELL,GENE,LEUKEMIA,PROGRESSION,ACTIVATION,CANCER,TRANSLATION,COMPLEXES}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{5902--5914}},
  title        = {{Large-scale circular RNA deregulation in T-ALL : unlocking unique ectopic expression of molecular subtypes}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2020002337}},
  volume       = {{4}},
  year         = {{2020}},
}

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