The trimeric transcription factor (TF) NF-Y regulates the CCAAT box, a DNA element enriched in promoters of genes overexpressed in many types of cancer. The regulatory NF-YA is present in two major isoforms, NF-YAl (“long”) and NF-YAs (“short”). There is growing indication that NF-YA levels are increased in tumors. Here, we report interrogation of RNA-Seq TCGA (The Cancer Genome Atlas)—all 576 samples—and GEO (Gene Expression Ominibus) datasets of lung adenocarcinoma (LUAD). NF-YAs is overexpressed in the three subtypes, proliferative, inflammatory, and TRU (terminal respiratory unit). CCAAT is enriched in promoters of tumor differently expressed genes (DEG) and in the proliferative/inflammatory intersection, matching with KEGG (Kyoto Encyclopedia of Genes and Genomes) terms cell-cycle and signaling. Increasing levels of NF-YAs are observed from low to high CpG island methylator phenotypes (CIMP). We identified 166 genes overexpressed in LUAD cell lines with low NF-YAs/NF-YAl ratios: applying this centroid to TCGA samples faithfully predicted tumors’ isoform ratio. This signature lacks CCAAT in promoters. Finally, progression-free intervals and hazard ratios concurred with the worst prognosis of patients with either a low or high NF-YAs/NF-YAl ratio. In conclusion, global overexpression of NF-YAs is documented in LUAD and is associated with aggressive tumor behavior; however, a similar prognosis is recorded in tumors with high levels of NF-YAl and overexpressed CCAAT-less genes.
NF-YA overexpression in lung cancer : LUAD / E. Bezzecchi, M. Ronzio, V. Semeghini, V. Andrioletti, R. Mantovani, D. Dolfini. - In: GENES. - ISSN 2073-4425. - 11:2(2020 Feb 14), pp. 198.1-198.17.
|Titolo:||NF-YA overexpression in lung cancer : LUAD|
BEZZECCHI, EUGENIA (Primo)
MANTOVANI, ROBERTO (Penultimo)
DOLFINI, DILETTA (Ultimo) (Corresponding)
|Parole Chiave:||Alternative splicings; CCAAT box; LUAD; Lung cancer; NF-YA; TCGA; Transcription factors|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Data di pubblicazione:||14-feb-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/genes11020198|
|Appare nelle tipologie:||01 - Articolo su periodico|