CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in TCF3::PBX1 ALL
Por:
Gutierrez-Camino A, Caron M, Richer C, Fuchs C, Illarregi U, Poncelet L, St-Onge P, Bataille AR, Tremblay-Dauphinais P, Lopez-Lopez E, Camós-Guijosa M, Ramirez-Orellana M, Astigarraga I, Lécuyer É, Bourque G, Martin-Guerrero I and Sinnett D
Publicada:
1 feb 2024
Ahead of Print:
25 ene 2024
Resumen:
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.
Filiaciones:
Gutierrez-Camino A:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Caron M:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada
Richer C:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Fuchs C:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Illarregi U:
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
Poncelet L:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
St-Onge P:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Bataille AR:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Tremblay-Dauphinais P:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Lopez-Lopez E:
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
Pediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain
Camós-Guijosa M:
Hematology Laboratory, Sant Joan de Déu Research Institute, Esplugues de Llobregat, 08950 Barcelona, Spain
Ramirez-Orellana M:
Department of Pediatric Hematology and Oncology, Niño Jesús University Hospital, 28009 Madrid, Spain
Astigarraga I:
Pediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain
Department of Pediatrics, Cruces University Hospital, 48903 Barakaldo, Spain
Lécuyer É:
Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada
Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montreal, QC H3C 3J7, Canada
Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada
Bourque G:
Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada
Martin-Guerrero I:
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
Pediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain
Sinnett D:
Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada
Green Submitted, gold
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