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miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 S expression
Ist Teil von
Open biology, 2024-02, Vol.14 (2), p.230319
Ort / Verlag
England
Erscheinungsjahr
2024
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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
). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1
, we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an
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-1
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-1
. 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-1
levels.