Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse NIH3T3 fibroblasts to investigate E2F1-regulated genes

ABSTRACT: Identification of E2F1-regulated genes that modulate the transition from quiescence into DNA synthesis, or have roles in apoptosis, signal transduction, membrane biology, and transcription repression.

ORGANISM(S): Mus musculus

SUBMITTER: William Douglas Cress

PROVIDER: E-GEOD-498 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of novel E2F1-regulated genes by microarray.

Ma Yihong Y Croxton Rhonda R Moorer Ronnie L RL Cress W Douglas WD

Archives of biochemistry and biophysics 20020301 2

The E2F pathway has been proposed to regulate genes involved in the transition from quiescence into DNA synthesis. However, this hypothesis has not been rigorously tested on a genomic scale. Toward this end, we have infected quiescent mouse fibroblasts, which do not express E2F1, with an E2F1-expressing adenovirus and examined the expression of more than 6000 genes using high-density microarrays. Microarray results clearly support the current paradigm; however, they suggest that E2F1 may also re ...[more]

PMID: 11888208

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Project description:Lung cancer is one of the most common and fatal cancer worldwide. There are two major types of lung cancer, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Recently, gefitinib, a small molecule, which target tyrosine kinase, has been regarded as the first-line treatment in NSCLC patients. However, several patients have been observed tumor recurrence and eventually developed progressive outcomes after target therapy. Thus, an effective therapeutic approach need to be explored. Here, we found that ectopically expressed ATP synthase on plasma membrane exhibited gefitinib-resistance properties in lung cancer cell lines. Furthermore, we unraveled that citreoviridin, an ectopic ATP synthase inhibitor, suppressed the abilities of both proliferation and colony formation in lung cancer cell lines. To elucidate the comprehensive mechanism regulated by citreoviridin, we performed microarray analysis. The results indicated that not only mRNAs but also long non-coding RNAs (lncRNAs) are involved in citreoviridin-treated cell death. One of the well-known lncRNAs, growth arrest-specific transcript (GAS5), was robustly upregulated after citreoviridin treatment. In order to investigate the upstream modulator of GAS5, we utilized chromatin immunoprecipitation (ChIP) assay and revealed that E2F transcription factor 1 (E2F1) could bind to the promoter of GAS5. Consistently, both microarray and qPCR data showed the expression level of E2F1 was negatively correlated to GAS5 after citreoviridin treatment. The evidence suggests that E2F1 might be a potential repressor of GAS5. Furthermore, combining microarray and Gene Set Enrichment Analysis (GSEA) analysis as well as qPCR demonstrated that p53 pathway was activated. To further realize the GAS5-p53 regulating network, RNA-protein pull-down assay followed by LC-MS/MS will be utilized to dissect the GAS5-interacting proteomic profiling.From the results, we identified 107 GAS5-interacting proteins in common from A549 and H1975 cell lines. Our proteomics experiments identified topoisomerase 2-alpha (TOP2A) as the key protein involved in the citreoviridin-regulated gefitinib-resistance pathway, therefore, we picked out TOP2A for further study. Additionally, we further validated the interaction between TOP2A and GAS5 by western blot and RNA immunoprecipitation (RIP). Taken together, this study suggests targeting E2F1/GAS5/p53 axis is a potential therapeutic strategy for gefitinib-resistant lung cancer.

Dataset Information

Transcription profiling of mouse NIH3T3 fibroblasts to investigate E2F1-regulated genes

Publications

Identification of novel E2F1-regulated genes by microarray.

Similar Datasets

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