Abstract
BackgroundWe present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction 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.MethodsWe 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 approach GeneNet. 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.ResultsThe 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.ConclusionIn 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.
Highlights
We present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction from transcriptomic microarray data
The minimum CLIP2 mRNA level was observed at 76 h with approximately 2.5% of the mRNA level compared to the non-transfected, identically treated control TPC-1 cells after 76 h
Western blot analysis revealed a broad range of CLIP2 protein levels in the different clones, which are in line with corresponding mRNA levels (Fig. 2)
Summary
We present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction from transcriptomic microarray data. The consequences of the Chernobyl nuclear accident enabled comprehensive studies of the epidemiologic effects of exposure to ionizing radiation and molecular characteristics of radiation induced malignancies. The results of these studies provide a valuable basis for current and future studies on radiation-associated thyroid carcinomas such as secondary cancers due to medical radiation exposure [4, 5]. Just a few years after the Chernobyl accident, an increased papillary thyroid carcinoma (PTC) incidence was observed in young children exposed to radiation related to a thyroid radiation dose mainly due to ingested iodine-131 [6,7,8,9,10,11,12]. The doses due to adverse radiation of non-target organs during radiotherapy were measured to be in the range of the investigated postChernobyl PTC and thereby promote the relevance of the derived results for medical radiation exposure and its adverse effects [25]
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