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Cancer Lett ; 591: 216880, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38621457

RESUMEN

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.


Asunto(s)
Biomarcadores de Tumor , Leucemia Mieloide Aguda , ARN Circular , Pronóstico , Humanos , Niño , ARN Circular/análisis , Biomarcadores de Tumor/análisis , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Análisis de Secuencia de ARN , Conjuntos de Datos como Asunto , Análisis de Supervivencia , Células K562 , Supervivencia sin Progresión , Resultado del Tratamiento , Preescolar , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica
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