{"owner": "ArrayExpress Uploader", "ownerprofile_id": "arrayexpress_sid", "species": "human", "factors": [{"GSM995513 1": {}}, {"GSM995512 1": {}}, {"GSM995511 1": {}}, {"GSM995510 1": {}}, {"GSM995509 1": {}}, {"GSM995508 1": {}}, {"GSM995507 1": {}}, {"GSM995506 1": {}}, {"GSM995505 1": {}}], "id": 2303, "pop_total": 0, "platform": 4, "summary_wrapped": "K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling...", "geo_gse_id": "E-GEOD-40517", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 0, "sample_count": 9, "tags": ["cancer", "cell", "genome", "lung", "lung cancer", "nsclc"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-40517_A-AFFY-44", "slug": "selective-requirement-for-mediator-med23-in-ras-ac", "geo_gds_id": "", "name": "Selective Requirement for Mediator MED23 in Ras-active Lung Cancer", "created": "Jul.12, 2014", "summary": "K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the \u201cRas-addiction\u201d of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells. The si-Ctrl, si-Med23 and si-Elk1 A549 cells were cultured in the normal condition. Then the cells were harvested for RNA extraction and hybridization on Affymetrix microarrays. The analysis contain 9 samples. si-Ctrl cells have three replicates (si-Ctrl#1, si-Ctrl#2 and si-Ctrl#3), and the si-Med23 or si-Elk1 group contains three different cell lines that harbor three different RNAi oligos against Med23 or Elk1 (si-Med23A, B, C and si-Elk1A, B, C).", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-40517", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-40517/samples/"}