دورية أكاديمية
Deletion of a pseudogene within a fragile site triggers the oncogenic expression of the mitotic CCSER1 gene.
| العنوان: | Deletion of a pseudogene within a fragile site triggers the oncogenic expression of the mitotic CCSER1 gene. |
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| المؤلفون: | Santoliquido BM; Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy., Frenquelli M; Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy., Contadini C; Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS-Regina Elena National Cancer Institute, Rome, Italy., Bestetti S; Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Gaviraghi M; Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy., Barbieri E; The Wistar Institute, Gene Expression and Regulation Program, Philadelphia, PA, USA., De Antoni A; DNA Metabolism Laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy., Albarello L; Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy., Amabile A; Vita-Salute San Raffaele University, Milan, Italy.; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy., Gardini A; The Wistar Institute, Gene Expression and Regulation Program, Philadelphia, PA, USA., Lombardo A; Vita-Salute San Raffaele University, Milan, Italy.; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy., Doglioni C; Vita-Salute San Raffaele University, Milan, Italy.; Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy., Provero P; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Department of Neurosciences 'Rita Levi Montalcini,' University of Torino, Turin, Italy., Soddu S; Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS-Regina Elena National Cancer Institute, Rome, Italy., Cittaro D; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Tonon G; Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy tonon.giovanni@hsr.it.; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy. |
| المصدر: | Life science alliance [Life Sci Alliance] 2021 Jun 29; Vol. 4 (8). Date of Electronic Publication: 2021 Jun 29 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]- |
| مواضيع طبية MeSH: | Chromosome Fragile Sites* , Gene Deletion* , Up-Regulation*, Cell Cycle Proteins/*genetics, Cell Line ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Genomic Instability ; HEK293 Cells ; HeLa Cells ; Humans ; Mitosis ; Pseudogenes |
| مستخلص: | The oncogenic role of common fragile sites (CFS), focal and pervasive gaps in the cancer genome arising from replicative stress, remains controversial. Exploiting the TCGA dataset, we found that in most CFS the genes residing within the associated focal deletions are down-regulated, including proteins involved in tumour immune recognition. In a subset of CFS, however, the residing genes are surprisingly overexpressed. Within the most frequent CFS in this group, FRA4F, which is deleted in up to 18% of cancer cases and harbours the CCSER1 gene, we identified a region which includes an intronic, antisense pseudogene, TMSB4XP8. TMSB4XP8 focal ablation or transcriptional silencing elicits the overexpression of CCSER1 , through a cis-acting mechanism. CCSER1 overexpression increases proliferation and triggers centrosome amplifications, multinuclearity, and aberrant mitoses. Accordingly, FRA4F is associated in patient samples to mitotic genes deregulation and genomic instability. As a result, cells overexpressing CCSER1 become sensitive to the treatment with aurora kinase inhibitors. Our findings point to a novel tumourigenic mechanism where focal deletions increase the expression of a new class of "dormant" oncogenes. (© 2021 Santoliquido et al.) |
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| معلومات مُعتمدة: | P30 CA010815 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (CCSER1 protein, human) 0 (Cell Cycle Proteins) |
| تواريخ الأحداث: | Date Created: 20210630 Date Completed: 20211208 Latest Revision: 20211214 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8321653 |
| DOI: | 10.26508/lsa.202101019 |
| PMID: | 34187875 |
| قاعدة البيانات: | MEDLINE |
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