| Autor: |
Raffaele Sessa, Silvia Trombetti, Alessandra Lo Bianco, Giovanni Amendola, Rosa Catapano, Elena Cesaro, Fara Petruzziello, Maria D'Armiento, Giuseppe Maria Maruotti, Giuseppe Menna, Paola Izzo, Michela Grosso |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Open Biology, Vol 14, Iss 2 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2046-2441 |
| DOI: |
10.1098/rsob.230319 |
| Popis: |
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-1S). 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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