: Aberrant splicing events are associated with colorectal cancer (CRC) and provide new opportunities for tumor diagnosis and treatment. The expression of the splice variants of NF-YA, the DNA binding subunit of the transcription factor NF-Y, is deregulated in multiple cancer types compared to healthy tissues. NF-YAs and NF-YAl isoforms differ in the transactivation domain, which may result in distinct transcriptional programs. In this study, we demonstrated that the NF-YAl transcript is higher in aggressive mesenchymal CRCs and predicts shorter patients' survival. In 2D and 3D conditions, CRC cells overexpressing NF-YAl (NF-YAlhigh) exhibit reduced cell proliferation, rapid single cell amoeboid-like migration, and form irregular spheroids with poor cell-to-cell adhesion. Compared to NF-YAshigh, NF-YAlhigh cells show changes in the transcription of genes involved in epithelial-mesenchymal transition, extracellular matrix and cell adhesion. NF-YAl and NF-YAs bind similarly to the promoter of the E-cadherin gene, but oppositely regulate its transcription. The increased metastatic potential of NF-YAlhigh cells in vivo was confirmed in zebrafish xenografts. These results suggest that the NF-YAl splice variant could be a new CRC prognostic factor and that splice-switching strategies may reduce metastatic CRC progression.

The NF-Y splicing signature controls hybrid EMT and ECM-related pathways to promote aggressiveness of colon cancer / Rigillo, Giovanna; Belluti, Silvia; Campani, Virginia; Ragazzini, Gregorio; Ronzio, Mirko; Miserocchi, Giacomo; Bighi, Beatrice; Cuoghi, Laura; Mularoni, Valentina; Zappavigna, Vincenzo; Dolfini, Diletta; Mercatali, Laura; Alessandrini, Andrea; Imbriano, Carol. - In: CANCER LETTERS. - ISSN 0304-3835. - 567:(2023), pp. 216262-216312. [10.1016/j.canlet.2023.216262]

The NF-Y splicing signature controls hybrid EMT and ECM-related pathways to promote aggressiveness of colon cancer

Rigillo, Giovanna;Belluti, Silvia;Campani, Virginia;Ragazzini, Gregorio;Bighi, Beatrice;Mularoni, Valentina;Zappavigna, Vincenzo;Imbriano, Carol
2023

Abstract

: Aberrant splicing events are associated with colorectal cancer (CRC) and provide new opportunities for tumor diagnosis and treatment. The expression of the splice variants of NF-YA, the DNA binding subunit of the transcription factor NF-Y, is deregulated in multiple cancer types compared to healthy tissues. NF-YAs and NF-YAl isoforms differ in the transactivation domain, which may result in distinct transcriptional programs. In this study, we demonstrated that the NF-YAl transcript is higher in aggressive mesenchymal CRCs and predicts shorter patients' survival. In 2D and 3D conditions, CRC cells overexpressing NF-YAl (NF-YAlhigh) exhibit reduced cell proliferation, rapid single cell amoeboid-like migration, and form irregular spheroids with poor cell-to-cell adhesion. Compared to NF-YAshigh, NF-YAlhigh cells show changes in the transcription of genes involved in epithelial-mesenchymal transition, extracellular matrix and cell adhesion. NF-YAl and NF-YAs bind similarly to the promoter of the E-cadherin gene, but oppositely regulate its transcription. The increased metastatic potential of NF-YAlhigh cells in vivo was confirmed in zebrafish xenografts. These results suggest that the NF-YAl splice variant could be a new CRC prognostic factor and that splice-switching strategies may reduce metastatic CRC progression.
2023
567
216262
216312
The NF-Y splicing signature controls hybrid EMT and ECM-related pathways to promote aggressiveness of colon cancer / Rigillo, Giovanna; Belluti, Silvia; Campani, Virginia; Ragazzini, Gregorio; Ronzio, Mirko; Miserocchi, Giacomo; Bighi, Beatrice; Cuoghi, Laura; Mularoni, Valentina; Zappavigna, Vincenzo; Dolfini, Diletta; Mercatali, Laura; Alessandrini, Andrea; Imbriano, Carol. - In: CANCER LETTERS. - ISSN 0304-3835. - 567:(2023), pp. 216262-216312. [10.1016/j.canlet.2023.216262]
Rigillo, Giovanna; Belluti, Silvia; Campani, Virginia; Ragazzini, Gregorio; Ronzio, Mirko; Miserocchi, Giacomo; Bighi, Beatrice; Cuoghi, Laura; Mularoni, Valentina; Zappavigna, Vincenzo; Dolfini, Diletta; Mercatali, Laura; Alessandrini, Andrea; Imbriano, Carol
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1307646
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