PloS one, 2020-05, Vol.15 (5), p.e0233380-e0233380
2020
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Details
- Autor(en) / Beteiligte
- Titel
- Aberrant expression of CPSF1 promotes head and neck squamous cell carcinoma via regulating alternative splicing
- Ist Teil von
- PloS one, 2020-05, Vol.15 (5), p.e0233380-e0233380
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2020
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- Alternative mRNA splicing increases protein diversity, and alternative splicing events (ASEs) drive oncogenesis in multiple tumor types. However, the driving alterations that underlie the broad dysregulation of ASEs are incompletely defined. Using head and neck squamous cell carcinoma (HNSCC) as a model, we hypothesized that the genomic alteration of genes associated with the spliceosome may broadly induce ASEs across a broad range of target genes, driving an oncogenic phenotype. We identified 319 spliceosome genes and employed a discovery pipeline to identify 13 candidate spliceosome genes altered in HNSCC using The Cancer Genome Atlas (TCGA) HNSCC data. Phenotypic screens identified amplified and overexpressed CPSF1 as a target gene alteration that was validated in proliferation, colony formation, and apoptosis assays in cell line and xenograft systems as well as in primary HNSCC. We employed knockdown and overexpression assays followed by identification of ASEs regulated by CPSF1 overexpression to identify changes in ASEs, and the expression of these ASEs was validated using RNA from cell line models. Alterations in expression of spliceosome genes, including CPSF1, may contribute to HNSCC by mediating aberrant ASE expression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0233380Titel-ID: cdi_plos_journals_2405599522
- Format
- –
- Schlagworte
- Alternative Splicing, Apoptosis, Bioinformatics, Biology, Biology and Life Sciences, Biomarkers, Tumor, Biotechnology, Cancer, Cancer genetics, Carcinogenesis, Carcinoma, Cell culture, Cell cycle, Cleavage And Polyadenylation Specificity Factor - genetics, Cleavage And Polyadenylation Specificity Factor - metabolism, Development and progression, EDTA, Gene expression, Gene Expression Regulation, Neoplastic, Genes, Genetic aspects, Genomes, Genomics, Head & neck cancer, Head and neck cancer, Head and Neck Neoplasms - genetics, Head and Neck Neoplasms - metabolism, Head and Neck Neoplasms - pathology, Health aspects, Human papillomavirus, Humans, Laboratories, Medicine and Health Sciences, Messenger RNA, mRNA, Mutation, Otolaryngology, Phenotypes, Research and Analysis Methods, RNA, RNA splicing, Squamous cell carcinoma, Squamous Cell Carcinoma of Head and Neck - genetics, Squamous Cell Carcinoma of Head and Neck - metabolism, Squamous Cell Carcinoma of Head and Neck - pathology, Surgery, Tumorigenesis, Tumors, Xenografts, Xenotransplantation