Genomic analysis of xCT-regulatory network in KSHV + primary effusion lymphomas.

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Even under conventional chemotherapy, PEL continues to portend nearly 100% mortality within several months, which urgently requires novel therapeutic strategies. We have previously demonstrated that targeting xCT, an amino acid transporter for cystine/glutamate exchange, induces significant PEL cell apoptosis through regulation of multiple host and viral factors [2]. More importantly, one of xCT selective inhibitors, Sulfasalazine (SASP), effectively prevents PEL tumor progression in an immune-deficient xenograft model [2]. In the current study, we use Illumina microarray to explore the profile of genes altered by SASP treatment within 3 KSHV + PEL cell-lines, and discover that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT Dai et al. (2015) [3]. The microarray original data have been submitted to Gene Expression Omnibus (GEO) database (Accession number: GSE65418).", "claims": [{"id": "claim-method", "statement": "Using the Illumina's GenomeStudio software, we normalized the signals using the “cubic spline algorithm” that assumes that the distribution of the transcript abundance is similar in all samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27081633", "locator": "sections[5] \"Microarray and data analysis\" paragraph 3", "quote": "Using the Illumina's GenomeStudio software, we normalized the signals using the “cubic spline algorithm” that assumes that the distribution of the transcript abundance is similar in all samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are publicly available", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27081633", "locator": "sections[1] \"p\" paragraph 1", "quote": "Data are publicly available"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Illumina microarray profiling of SASP-treated PEL cell lines identified potentially xCT-regulated genes involved in oxidative stress/antioxidant defense, apoptosis/anti-apoptosis/cell death, and responses to unfolded or topologically incorrect proteins; the raw data are publicly available through GEO accession GSE65418 at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65418.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27081633", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In the current study, we use Illumina microarray to explore the profile of genes altered by SASP treatment within 3 KSHV + PEL cell-lines, and discover that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT Dai et al. (2015) [3]."}, {"asset": "source:pmid:27081633", "locator": "sections[5] \"Microarray and data analysis\" paragraph 3", "quote": "Using the Illumina's GenomeStudio software, we normalized the signals using the “cubic spline algorithm” that assumes that the distribution of the transcript abundance is similar in all samples."}, {"asset": "source:pmid:27081633", "locator": "sections[2] \"Direct link to deposited data\" paragraph 2", "quote": "http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65418."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Illumina microarray profiling of SASP-treated PEL cell lines identified potentially xCT-regulated genes involved in oxidative stress/antioxidant defense, apoptosis/anti-apoptosis/cell death, and responses to unfolded or topologically incorrect proteins; the raw data are publicly available through GEO accession GSE65418 at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65418.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:27081633"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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