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Open AccessArticle

NF-YA Overexpression in Lung Cancer: LUAD

1
Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy
2
Internal Medicine VIII, University Hospital Tübingen. Otfried-Müller-Str. 14, 72076 Tübingen, Germany
*
Author to whom correspondence should be addressed.
Genes 2020, 11(2), 198; https://doi.org/10.3390/genes11020198 (registering DOI)
Received: 4 February 2020 / Accepted: 10 February 2020 / Published: 14 February 2020
(This article belongs to the Section Molecular Genetics and Genomics)
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. View Full-Text
Keywords: lung cancer; LUAD; transcription factors; TCGA; CCAAT box; NF-YA; alternative splicings lung cancer; LUAD; transcription factors; TCGA; CCAAT box; NF-YA; alternative splicings
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Bezzecchi, E.; Ronzio, M.; Semeghini, V.; Andrioletti, V.; Mantovani, R.; Dolfini, D. NF-YA Overexpression in Lung Cancer: LUAD. Genes 2020, 11, 198.

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