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CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and
Angela Gutierrez-Camino1, Maxime Caron1,2, Chantal Richer1
1Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada.
International Journal of Molecular Sciences
|February 10, 2024
Summary
Circular RNAs (circRNAs) can stratify childhood B-cell acute lymphoblastic leukemia (B-ALL) subtypes. Specific circRNAs, like circBARD1, may drive B-ALL pathogenesis by influencing key signaling pathways.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Childhood B-cell acute lymphoblastic leukemia (B-ALL) is diverse, with molecular subgroups.
- Circular RNAs (circRNAs) are novel non-coding RNAs implicated in cancer, but their role in B-ALL is unclear.
Purpose of the Study:
- To investigate the potential of circRNAs as biomarkers for stratifying childhood B-ALL subtypes.
- To identify specific circRNAs and their regulatory mechanisms in B-ALL pathogenesis.
Main Methods:
- RNA sequencing (RNA-seq) on 105 childhood B-ALL patients across six genetic subtypes and seven controls.
- Differential expression analysis to identify subtype-specific circRNAs.
- CRISPR-Cas13d system for functional characterization of circRNAs.
Main Results:
- CircRNAs effectively stratified B-ALL subtypes, with distinct expression profiles.
- 156 overexpressed and 134 underexpressed circRNAs were identified, many unique to specific subtypes.
- The TCF3::PBX1 subtype showed the highest number of unique, overexpressed circRNAs, identifiable by a circRNA signature.
- NUDT21, an RNA-binding protein, may contribute to circRNA enrichment in the TCF3::PBX1 subtype.
- circBARD1, regulated by NUDT21, was implicated in leukemogenesis via the p38 pathway and hsa-miR-153-5p.
Conclusions:
- CircRNAs serve as valuable biomarkers for classifying childhood B-ALL subtypes.
- Specific circRNAs, such as circBARD1, may play a functional role in B-ALL development.
- Understanding circRNA regulation offers potential therapeutic targets for B-ALL.
