NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing, NF-YAl and NF-YAs, which differ in the transactivation domain. Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer (CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patients’ survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by the worst prognosis. Through the analysis of 3D cellular models, we demonstrated that altered expression of genes related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl in metabolic flexibility of cancer cells that adjust their metabolism in response to environmental changes to potentiate migration. The zebrafish xenograft model confirmed the metastatic potential triggered by NF-YAl in CRC cells. Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination.

Dysregulation of NF–Y splicing drives metabolic rewiring and aggressiveness in colon cancer / Belluti, S.; Mularoni, V.; Campani, Virginia; Rigillo, G.; Cuoghi, L.; Ronzio, M.; Miserocchi, G.; Dolfini, D.; Righi, Valeria; Alessandrini, A.; Zappavigna, V.; Imbriano, C.. - (2023). (Intervento presentato al convegno Joint Meeting AGI_SIMAG 2023 - Associazione Genetica Italiana tenutosi a Cortona nel 14-16 settembre 2023).

Dysregulation of NF–Y splicing drives metabolic rewiring and aggressiveness in colon cancer

S. Belluti;V. Mularoni;Virginia Campani;G. Rigillo;L. Cuoghi;A. Alessandrini;V. Zappavigna;C. Imbriano
2023

Abstract

NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing, NF-YAl and NF-YAs, which differ in the transactivation domain. Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer (CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patients’ survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by the worst prognosis. Through the analysis of 3D cellular models, we demonstrated that altered expression of genes related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl in metabolic flexibility of cancer cells that adjust their metabolism in response to environmental changes to potentiate migration. The zebrafish xenograft model confirmed the metastatic potential triggered by NF-YAl in CRC cells. Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination.
2023
Joint Meeting AGI_SIMAG 2023 - Associazione Genetica Italiana
Cortona
14-16 settembre 2023
Belluti, S.; Mularoni, V.; Campani, Virginia; Rigillo, G.; Cuoghi, L.; Ronzio, M.; Miserocchi, G.; Dolfini, D.; Righi, Valeria; Alessandrini, A.; Zapp...espandi
File in questo prodotto:
File Dimensione Formato  
Book of Abstract Poster 2023 56.pdf

Open access

Tipologia: Abstract
Dimensione 193.82 kB
Formato Adobe PDF
193.82 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1319067
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact