ArticleMolecular cancer2012
Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells.
Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 69 citations in OpenAlex.
- Optimizing Recombinant Protein Production in CHO Cells by Silencing the Caspase 8 Associated Protein 2 Gene via the CRISPR-Cas9 System.Molecular biotechnology · 2026Article
- Natural language processing of gene descriptions for overrepresentation analysis with GeneTEA.Genome biology · 2025Article
- Dual role of CASP8AP2/FLASH in regulating epithelial-to-mesenchymal transition plasticity (EMP).Translational oncology · 2024Article
- Knockout of the caspase 8-associated protein 2 gene improves recombinant protein expression in HEK293 cells through up-regulation of the cyclin-dependent kinase inhibitor 2A gene.Biotechnology and bioengineering · 2021Article
- Systematic mutation analysis in rare colorectal cancer presenting ovarian metastases.Scientific reports · 2019Article
- Replication-dependent histone isoforms: a new source of complexity in chromatin structure and function.Nucleic acids research · 2018Review
- Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations.BMC cancer · 2018Article
- Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.Cell cycle (Georgetown, Tex.) · 2017Article
- FLASH protects ZEB1 from degradation and supports cancer cells' epithelial-to-mesenchymal transition.Oncogenesis · 2016Article
- p53 checkpoint ablation exacerbates the phenotype of Hinfp dependent histone H4 deficiency.Cell cycle (Georgetown, Tex.) · 2015Article
- High expression of protein phosphatase 4 is associated with the aggressive malignant behavior of colorectal carcinoma.Molecular cancer · 2015Article
- mTOR kinase inhibitors synergize with histone deacetylase inhibitors to kill B-cell acute lymphoblastic leukemia cells.Oncotarget · 2015Article
- Novel strategies to enforce an epithelial phenotype in mesenchymal cells.Cancer research · 2014Article
- Fidelity of histone gene regulation is obligatory for genome replication and stability.Molecular and cellular biology · 2014Article
- FLASH/casp8ap2 is indispensable for early embryogenesis but dispensable for proliferation and differentiation of ES cells.PloS one · 2014Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundColorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival.
resultsA small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/ß-catenin pathway.
conclusionsWe have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH.
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