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Transcriptome network of the papillary thyroid carcinoma radiation marker CLIP2.
Radiat. Oncol. 15:182 (2020)
Background: We present a functional gene association network of the CLIP2 gene, generated byde-novoreconstruction from transcriptomic microarray data. CLIP2 was previously identified as a potential marker for radiation induced papillary thyroid carcinoma (PTC) of young patients in the aftermath of the Chernobyl reactor accident. Considering the rising thyroid cancer incidence rates in western societies, potentially related to medical radiation exposure, the functional characterization of CLIP2 is of relevance and contributes to the knowledge about radiation-induced thyroid malignancies.Methods: We generated a transcriptomic mRNA expression data set from a CLIP2-perturbed thyroid cancer cell line (TPC-1) with induced CLIP2 mRNA overexpression and siRNA knockdown, respectively, followed by gene-association network reconstruction using the partial correlation-based approachGeneNet. Furthermore, we investigated different approaches for prioritizing differentially expressed genes for network reconstruction and compared the resulting networks with existing functional interaction networks from the Reactome, Biogrid and STRING databases. The derived CLIP2 interaction partners were validated on transcript and protein level.Results: The best reconstructed network with regard to selection parameters contained a set of 20 genes in the 1st neighborhood of CLIP2 and suggests involvement of CLIP2 in the biological processes DNA repair/maintenance, chromosomal instability, promotion of proliferation and metastasis. Peptidylprolyl Isomerase Like 3 (PPIL3), previously identified as a potential direct interaction partner of CLIP2, was confirmed in this study by co-expression at the transcript and protein level.Conclusion:In our study we present an optimized preselection approach for genes subjected to gene- association network reconstruction, which was applied to CLIP2 perturbation transcriptome data of a thyroid cancer cell culture model. Our data support the potential carcinogenic role of CLIP2 overexpression in radiation-induced PTC and further suggest potential interaction partners of the gene.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Post-chernobyl; Cancer Risk; Cell-proliferation; Colorectal-cancer; Cop9 Signalosome; Aurora-a; Expression; Dna; Signature; Biomarker
ISSN (print) / ISBN
1748-717X
e-ISSN
1748-717X
Journal
Radiation Oncology
Quellenangaben
Volume: 15,
Issue: 1,
Article Number: 182
Publisher
BioMed Central
Publishing Place
Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Translational Metabolic Oncology (TMO)
Institute of Radiation Biology (ISB)
Institute of Molecular Toxicology and Pharmacology (TOXI)
CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Institute of Radiation Biology (ISB)
Institute of Molecular Toxicology and Pharmacology (TOXI)
CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Grants
Helmholtz München