NF-Y is a pioneer trimeric transcription factor formed by the Histone Fold Domain (HFD) NF-YB/NF-YC subunits and NF-YA. Three subunits are required for DNA binding. CCAAT-specificity resides in NF-YA and transactivation resides in Q-rich domains of NF-YA and NF-YC. They are involved in alternative splicing (AS). We recently showed that NF-YA is overexpressed in breast and lung carcinomas. We report here on the overexpression of all subunits in the liver hepatocellular carcinoma (HCC) TCGA database, specifically the short NF-YAs and NF-YC2 (37 kDa) isoforms. This is observed at all tumor stages, in viral-infected samples and independently from the inflammatory status. Up-regulation of NF-YAs and NF-YC, but not NF-YB, is associated to tumors with mutant p53. We used a deep-learning-based method (DeepCC) to extend the partitioning of the three molecular clusters to all HCC TCGA tumors. In iCluster3, CCAAT is a primary matrix found in promoters of up-regulated genes, and cell-cycle pathways are enriched. Finally, clinical data indicate that, globally, only NF-YAs, but not HFD subunits, correlate with the worst prognosis; in iCluster1 patients, however, all subunits correlate. The data show a difference with other epithelial cancers, in that global overexpression of the three subunits is reported and clinically relevant in a subset of patients; yet, they further reinstate the regulatory role of the sequence-specific subunit.
NF-Y Overexpression in Liver Hepatocellular Carcinoma (HCC) / E. Bezzecchi, M. Ronzio, R. Mantovani, D. Dolfini. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:23(2020 Dec 01), pp. 9157.1-9157.16.
|Titolo:||NF-Y Overexpression in Liver Hepatocellular Carcinoma (HCC)|
MANTOVANI, ROBERTO (Penultimo)
DOLFINI, DILETTA (Ultimo)
|Parole Chiave:||HCC; NF-Y; Transcription Factors; TCGA; CCAAT box|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Data di pubblicazione:||1-dic-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/ijms21239157|
|Appare nelle tipologie:||01 - Articolo su periodico|