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| Status |
Public on Jan 28, 2023 |
| Title |
High levels of NF-YAl drives EMT in Claudinlow tumors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
NF-Y is a trimeric transcription factor whose binding site -the CCAAT box- is enriched in cancer-promoting genes. The regulatory subunit, the sequence-specificity conferring NF-YA, comes in two major isoforms, NF-YA long (NF-YAl) and short (NF-YAs). Extensive expression analysis in epithelial cancers determined two features: widespread overexpression and changes in NF-YAl/NF-Ys ratios (NF-YAr) in tumors with EMT features. We performed wet and in silico experiments to explore the role of the NF-YA isoforms in breast -BRCA- and gastric -STAD- cancers. We generated clones of two Claudinlow BRCA lines BT549 and SUM159PT ablated of exon-3, thus shifting expression from NF-YAl to NF-YAs. Edited clones show normal growth, but reduced migratory capacities in vitro, and ability to metastatize in vivo. Using TCGA, including upon deconvolution of scRNA-seq data, we formalize the clinical importance of high NF-YAr, associated to EMT genes and cell populations. We derive a novel, 158 genes signature common to BRCA and STAD Claudinlow tumors. Finally, we identify splicing factors associated to high NF-YAr, further validating RBFOX2 as promoting expression of NF-YAl with wet experiments. In conclusion, these data bring three relevant results: (i) concerning Claudinlow tumors, the definition and clinical implications of NF-YAr and the 158 genes signature; (ii) genetic evidence of a role of exon-3 28 aminoacids, empowering NF-YAl with EMT-driving features in BRCA. (iii) The definition of a set of splicing factors fine-tuning the levels of NF-YA isoforms.
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| Overall design |
Comparison of gene- and isoform-level expression of RNA-seq data between SUM159PT and BT549 WT cell lines and two NF-YA ΔEx3 edited clones for each cell line. Samples for all the conditions were obtained by three independent biological replicates.
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| Contributor(s) |
Londero M, Gallo A, Dolfini D |
| Citation(s) |
36707502 |
| Submission date |
Jul 13, 2022 |
| Last update date |
Feb 10, 2023 |
| Contact name |
Alberto Gallo |
| E-mail(s) |
alberto.gallo1@unimi.it
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| Phone |
3478054509
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| Organization name |
Università degli Studi di Milano
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| Street address |
Via Marconi 11/B
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| City |
Ceriano Laghetto |
| State/province |
District Of Columbia |
| ZIP/Postal code |
20816 |
| Country |
Italy |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA858254 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE208088_final_tab_BT549_norm_genes.txt.gz |
508.9 Kb |
(ftp)(http) |
TXT |
| GSE208088_final_tab_BT549_norm_isoforms.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE208088_final_tab_BT549_raw_genes.txt.gz |
522.2 Kb |
(ftp)(http) |
TXT |
| GSE208088_final_tab_SUM159PT_norm_genes.txt.gz |
497.2 Kb |
(ftp)(http) |
TXT |
| GSE208088_final_tab_SUM159_norm_isoforms.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE208088_final_tab_SUM159_raw_genes.txt.gz |
520.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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