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: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/3/1477 |
| Summary: | 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. |
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| ISSN: | 1661-6596 1422-0067 |