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Open AccessArticle

NF-YA Overexpression in Lung Cancer: LUSC

Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy
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Genes 2019, 10(11), 937; https://doi.org/10.3390/genes10110937
Received: 12 September 2019 / Revised: 4 November 2019 / Accepted: 13 November 2019 / Published: 17 November 2019
(This article belongs to the Section Molecular Genetics and Genomics)
The CCAAT box is recognized by the trimeric transcription factor NF-Y, whose NF-YA subunit is present in two major splicing isoforms, NF-YAl (“long”) and NF-YAs (“short”). Little is known about the expression levels of NF-Y subunits in tumors, and nothing in lung cancer. By interrogating RNA-seq TCGA and GEO datasets, we found that, unlike NF-YB/NF-YC, NF-YAs is overexpressed in lung squamous cell carcinomas (LUSC). The ratio of the two isoforms changes from normal to cancer cells, with NF-YAs becoming predominant in the latter. NF-YA increased expression correlates with common proliferation markers. We partitioned all 501 TCGA LUSC tumors in the four molecular cohorts and verified that NF-YAs is similarly overexpressed. We analyzed global and subtype-specific RNA-seq data and found that CCAAT is the most abundant DNA matrix in promoters of genes overexpressed in all subtypes. Enriched Gene Ontology terms are cell-cycle and signaling. Survival curves indicate a worse clinical outcome for patients with increasing global amounts of NF-YA; same with hazard ratios with very high and, surprisingly, very low NF-YAs/NF-YAl ratios. We then analyzed gene expression in this latter cohort and identified a different, pro-migration signature devoid of CCAAT. We conclude that overexpression of the NF-Y regulatory subunit in LUSC has the scope of increasing CCAAT-dependent, proliferative (NF-YAshigh) or CCAAT-less, pro-migration (NF-YAlhigh) genes. The data further reinstate the importance of analysis of single isoforms of TFs involved in tumor development. View Full-Text
Keywords: lung cancer; LUSC; transcription factors; TCGA; CCAAT box; NF-YA; alternative splicing lung cancer; LUSC; transcription factors; TCGA; CCAAT box; NF-YA; alternative splicing
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Bezzecchi, E.; Ronzio, M.; Dolfini, D.; Mantovani, R. NF-YA Overexpression in Lung Cancer: LUSC. Genes 2019, 10, 937.

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