Nf-y subunits overexpression in hnscc

Eugenia Bezzecchi, Andrea Bernardini, Mirko Ronzio, Claudia Miccolo, Susanna Chiocca, Diletta Dolfini, Roberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

NF-Y is the CCAAT-binding trimer formed by the histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box is generally prevalent in promoters of “cancer” genes. We reported the overexpression of NF-YA in BRCA, LUAD and LUSC, and of all subunits in HCC. Altered splicing of NF-YA was found in breast and lung cancer. We analyzed RNA-seq datasets of TCGA and cell lines of head and neck squamous cell carcinomas (HNSCC). We partitioned all TCGA data into four subtypes, deconvoluted single-cell RNA-seq of tumors and derived survival curves. The CCAAT box was enriched in the promoters of overexpressed genes. The “short” NF-YAs was overexpressed in all subtypes and the “long” NF-YAl in Mesenchymal. The HFD subunits are overexpressed, except Basal (NF-YB) and Atypical (NF-YC); NF-YAl is increased in p53 mutated tumors. In HPV-positive tumors, high levels of NF-YAs, p16 and ∆Np63 correlate with better prognosis. Deconvolution of single cell RNA-seq (scRNA-seq) found a correlation of NF-YAl with Cancer Associated Fibroblasts (CAFs) and p-EMT cells, a population endowed with metastatic potential. We conclude that overexpression of HFD subunits and NF-YAs is protective in HPV-positive tumors; expression of NF-YAl is largely confined to mutp53 tumors and malignant p-EMT cells.

Original languageEnglish
Article number3019
JournalCancers
Volume13
Issue number12
DOIs
Publication statusPublished - Jun 2 2021

Keywords

  • Alternative splicing
  • CCAAT box
  • HNSCC
  • NF-Y
  • TCGA
  • Transcription factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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