Small RNA-seq in children and young adults with T-cell acute lymphoblastic leukemia identifies miR-143-3p as candidate tumor suppressor with potential therapeutic implications

The aim of the study was to identify miRNAs and pathways specifically deregulated in adolescents and young adult patients (AYA, defined as patients at the age of 15-39 years, at diagnosis) with T-cell acute lymphoblastic leukemia (T-ALL). Small RNA-seq showed no major differences between AYA and pediatric T-ALL (<15 years of age). Yet, it revealed consistent downregulation of miR-143-3p in T-ALL patients, both children and AYA. Prediction algorithms showed known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, FGF9, and MAP3K7. Pathway analysis revealed signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells via insufficient silencing of oncogenes implicated in these pathways.