| Autor: |
Gutierrez-Camino, Angela, Caron, Maxime, Richer, Chantal, Fuchs, Claire, Illarregi, Unai, Poncelet, Lucas, St-Onge, Pascal, Bataille, Alain R., Tremblay-Dauphinais, Pascal, Lopez-Lopez, Elixabet, Camos, Mireia, Ramirez-Orellana, Manuel, Astigarraga, Itziar, Lécuyer, Éric, Bourque, Guillaume, Martin-Guerrero, Idoia, Sinnett, Daniel |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences; Feb2024, Vol. 25 Issue 3, p1477, 14p |
| Abstrakt: |
Childhood B-cell acute lymphoblastic leukemia (B-ALL) is a heterogeneous disease comprising multiple molecular subgroups with subtype-specific expression profiles. Recently, a new type of ncRNA, termed circular RNA (circRNA), has emerged as a promising biomarker in cancer, but little is known about their role in childhood B-ALL. Here, through RNA-seq analysis in 105 childhood B-ALL patients comprising six genetic subtypes and seven B-cell controls from two independent cohorts we demonstrated that circRNAs properly stratified B-ALL subtypes. By differential expression analysis of each subtype vs. controls, 156 overexpressed and 134 underexpressed circRNAs were identified consistently in at least one subtype, most of them with subtype-specific expression. TCF3::PBX1 subtype was the one with the highest number of unique and overexpressed circRNAs, and the circRNA signature could effectively discriminate new patients with TCF3::PBX1 subtype from others. Our results indicated that NUDT21, an RNA-binding protein (RBP) involved in circRNA biogenesis, may contribute to this circRNA enrichment in TCF3::PBX1 ALL. Further functional characterization using the CRISPR-Cas13d system demonstrated that circBARD1, overexpressed in TCF3::PBX1 patients and regulated by NUDT21, might be involved in leukemogenesis through the activation of p38 via hsa-miR-153-5p. Our results suggest that circRNAs could play a role in the pathogenesis of childhood B-ALL. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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