1. miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 S expression.
- Author
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Sessa R, Trombetti S, Bianco AL, Amendola G, Catapano R, Cesaro E, Petruzziello F, D'Armiento M, Maruotti GM, Menna G, Izzo P, and Grosso M
- Subjects
- Humans, Down Syndrome genetics, Down Syndrome complications, Down Syndrome pathology, Leukemia, Myeloid genetics, Leukemia, Myeloid metabolism, Leukemia, Myeloid pathology, Leukemoid Reaction complications, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1
S ). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1S , we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1S . These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1S levels.- Published
- 2024
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