: 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.
miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1S expression / Sessa, Raffaele; Trombetti, Silvia; Bianco, Alessandra Lo; Amendola, Giovanni; Catapano, Rosa; Cesaro, Elena; Petruzziello, Fara; D'Armiento, Maria; Maruotti, Giuseppe Maria; Menna, Giuseppe; Izzo, Paola; Grosso, Michela. - In: OPEN BIOLOGY. - ISSN 2046-2441. - 14:2(2024). [10.1098/rsob.230319]
miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1S expression
Sessa, RaffaelePrimo
;Trombetti, SilviaSecondo
;Bianco, Alessandra Lo;Catapano, Rosa;Cesaro, Elena;Petruzziello, Fara;D'Armiento, Maria;Maruotti, Giuseppe Maria;Izzo, Paola;Grosso, Michela
Ultimo
2024
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-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.File | Dimensione | Formato | |
---|---|---|---|
rsob.230319.pdf
accesso aperto
Licenza:
Dominio pubblico
Dimensione
1.53 MB
Formato
Adobe PDF
|
1.53 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.