Authors
Monika Drobna-Sledzinska, Alessia Buratin, Eleonora Roncaglia, Alberto Caregari, Ilias Glogovitis, Maria Kosmalska, Xing Zhao, Silvia Bresolin, Enrico Gaffo, Anke Van den Berg, Joost Kluiver, Malgorzata Dawidowska, Stefania Bortoluzzi
Published in
Leukemia. Jul 27, 2026. Epub Jul 27, 2026.
Abstract
Circular RNAs constitute an emerging area of intensive research in cancer. In T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematologic malignancy characterized by clonal proliferation of T-cell precursors, the function of most aberrantly expressed circRNAs is not yet understood. To identify circRNAs acting as miRNA sponges, we performed AGO2 immunoprecipitation and RNA sequencing (AGO2-RIP-seq) in four T-ALL cell lines. Our analysis revealed circRNAs consistently enriched in the AGO2-bound fraction, highlighting a new resource for T-ALL research. Notably, circRNAs were more enriched (7.3%) compared to linear RNAs (3%). For functional investigation, we focused on the most abundant AGO2-bound circRNAs that were also found to be dysregulated in T-ALL patients. Knockdown of circN4BP2L2 revealed its ability to promote cell proliferation and confer resistance to apoptosis in T-ALL cell lines, in addition to modulating key T-ALL pathogenic pathways. Analysis of gene expression of T-ALL patients disclosed peculiar features of T-ALL with high circN4BP2L2 expression. A marked overlap was observed between differentially expressed genes upon knockdown of circN4BP2L2 in vitro and the profiles of circN4BP2L2 stratified T-ALL cases. This work provides new insights into the circRNA-mediated regulatory networks driving this malignancy and presents circN4BP2L2 as a key RNA shaping oncogenic phenotype in T-ALL.
PMID:
42509253
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.
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