CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/3/1477 |
| _version_ | 1797318768143106048 |
|---|---|
| author | Angela Gutierrez-Camino Maxime Caron Chantal Richer Claire Fuchs Unai Illarregi Lucas Poncelet Pascal St-Onge Alain R. Bataille Pascal Tremblay-Dauphinais Elixabet Lopez-Lopez Mireia Camos Manuel Ramirez-Orellana Itziar Astigarraga Éric Lécuyer Guillaume Bourque Idoia Martin-Guerrero Daniel Sinnett |
| author_facet | Angela Gutierrez-Camino Maxime Caron Chantal Richer Claire Fuchs Unai Illarregi Lucas Poncelet Pascal St-Onge Alain R. Bataille Pascal Tremblay-Dauphinais Elixabet Lopez-Lopez Mireia Camos Manuel Ramirez-Orellana Itziar Astigarraga Éric Lécuyer Guillaume Bourque Idoia Martin-Guerrero Daniel Sinnett |
| author_sort | Angela Gutierrez-Camino |
| collection | DOAJ |
| description | 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. <i>TCF3::PBX1</i> subtype was the one with the highest number of unique and overexpressed circRNAs, and the circRNA signature could effectively discriminate new patients with <i>TCF3::PBX1</i> subtype from others. Our results indicated that <i>NUDT21</i>, an RNA-binding protein (RBP) involved in circRNA biogenesis, may contribute to this circRNA enrichment in <i>TCF3::PBX1</i> ALL. Further functional characterization using the CRISPR-Cas13d system demonstrated that <i>circBARD1</i>, overexpressed in <i>TCF3::PBX1</i> patients and regulated by <i>NUDT21</i>, might be involved in leukemogenesis through the activation of p38 via <i>hsa-miR-153-5p</i>. Our results suggest that circRNAs could play a role in the pathogenesis of childhood B-ALL. |
| first_indexed | 2024-03-08T03:56:07Z |
| format | Article |
| id | doaj.art-e3bdca681b954271a19f7a92bf315bde |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:56:07Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e3bdca681b954271a19f7a92bf315bde2024-02-09T15:13:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253147710.3390/ijms25031477CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALLAngela Gutierrez-Camino0Maxime Caron1Chantal Richer2Claire Fuchs3Unai Illarregi4Lucas Poncelet5Pascal St-Onge6Alain R. Bataille7Pascal Tremblay-Dauphinais8Elixabet Lopez-Lopez9Mireia Camos10Manuel Ramirez-Orellana11Itziar Astigarraga12Éric Lécuyer13Guillaume Bourque14Idoia Martin-Guerrero15Daniel Sinnett16Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDepartment of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainHematology Laboratory, Sant Joan de Déu Research Institute, Esplugues de Llobregat, 08950 Barcelona, SpainDepartment of Pediatric Hematology and Oncology, Niño Jesús University Hospital, 28009 Madrid, SpainPediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, SpainInstitut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, CanadaDepartment of Human Genetics, McGill University, Montreal, QC H3A 0G4, CanadaDepartment of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDivision of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, CanadaChildhood 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. <i>TCF3::PBX1</i> subtype was the one with the highest number of unique and overexpressed circRNAs, and the circRNA signature could effectively discriminate new patients with <i>TCF3::PBX1</i> subtype from others. Our results indicated that <i>NUDT21</i>, an RNA-binding protein (RBP) involved in circRNA biogenesis, may contribute to this circRNA enrichment in <i>TCF3::PBX1</i> ALL. Further functional characterization using the CRISPR-Cas13d system demonstrated that <i>circBARD1</i>, overexpressed in <i>TCF3::PBX1</i> patients and regulated by <i>NUDT21</i>, might be involved in leukemogenesis through the activation of p38 via <i>hsa-miR-153-5p</i>. Our results suggest that circRNAs could play a role in the pathogenesis of childhood B-ALL.https://www.mdpi.com/1422-0067/25/3/1477acute lymphoblastic leukemiachildhood B-ALLcircular RNA<i>TCF3::PBX1</i>RNA-binding protein<i>NUDT21</i> |
| spellingShingle | Angela Gutierrez-Camino Maxime Caron Chantal Richer Claire Fuchs Unai Illarregi Lucas Poncelet Pascal St-Onge Alain R. Bataille Pascal Tremblay-Dauphinais Elixabet Lopez-Lopez Mireia Camos Manuel Ramirez-Orellana Itziar Astigarraga Éric Lécuyer Guillaume Bourque Idoia Martin-Guerrero Daniel Sinnett CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL International Journal of Molecular Sciences acute lymphoblastic leukemia childhood B-ALL circular RNA <i>TCF3::PBX1</i> RNA-binding protein <i>NUDT21</i> |
| title | CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL |
| title_full | CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL |
| title_fullStr | CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL |
| title_full_unstemmed | CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL |
| title_short | CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in <i>TCF3::PBX1</i> ALL |
| title_sort | circrnaome of childhood acute lymphoblastic leukemia deciphering subtype specific expression profiles and involvement in i tcf3 pbx1 i all |
| topic | acute lymphoblastic leukemia childhood B-ALL circular RNA <i>TCF3::PBX1</i> RNA-binding protein <i>NUDT21</i> |
| url | https://www.mdpi.com/1422-0067/25/3/1477 |
| work_keys_str_mv | AT angelagutierrezcamino circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT maximecaron circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT chantalricher circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT clairefuchs circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT unaiillarregi circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT lucasponcelet circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT pascalstonge circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT alainrbataille circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT pascaltremblaydauphinais circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT elixabetlopezlopez circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT mireiacamos circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT manuelramirezorellana circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT itziarastigarraga circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT ericlecuyer circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT guillaumebourque circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT idoiamartinguerrero circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall AT danielsinnett circrnaomeofchildhoodacutelymphoblasticleukemiadecipheringsubtypespecificexpressionprofilesandinvolvementinitcf3pbx1iall |