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Identification of target genes regulated by ΔNp63α in SaOS-2 cells stably expressed with ΔNp63α

ABSTRACT: To identify the target gene of ΔNp63α, in osteosarcoma cells, we performed the global gene expression profiling in SaOS- 2 cells stably overexpressing the ΔNp63α gene (SaOS- 2-ΔNp63α). ΔNp63α target genes were identified by comparison with genes expressed from SaOS-2-EV transfected with an empty vector ( SaOS-2-EV).

ORGANISM(S): Homo sapiens

PROVIDER: GSE54942 | GEO | 2014/02/27

SECONDARY ACCESSION(S): PRJNA239403

REPOSITORIES: GEO

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Project description:A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. Two cell lines are compared, which are Saos-2 osteosarcoma cells sensitive to methotrexate and Saos-2 cells resistant to 10e-6M methotrexate. Six samples are provided which correspond to triplicates of each cell line. The samples provided were analyzed using the specific software GeneSpring GX.

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Identification of target genes regulated by ΔNp63α in SaOS-2 cells stably expressed with ΔNp63α

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