Role of long non-coding RNAs in sarcoma pathogenesis
Role of long non-coding RNAs in sarcoma pathogenesis
批准号:
9883636
负责人:
Eric Alejandro Sweet-Cordero
金额:
$37.6万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-03-13 至 2022-02-28
关键词:
Adolescent and Young AdultAgarAutomobile DrivingBindingBiochemicalBiologicalBiological ModelsCancer BiologyCell LineCellsChIP-seqChildChromatinColon CarcinomaDNADNA BindingDataDiseaseEnhancersEventEwings sarcomaExclusionFLI1 Transcription FactorFamilyGene ExpressionGene Expression RegulationGenesGeneticGenomicsGoalsGrowthHistonesIn VitroLeadMaintenanceMalignant NeoplasmsMalignant neoplasm of prostateMediatingMesenchymal DifferentiationModelingMolecularMorbidity - disease rateOncogenicPathogenesisPatientsPatternProteinsProteomicsRNARNA-Binding Protein EWSRNA-Binding ProteinsRoleSiteTestingTranscriptTumor SuppressionUntranslated RNAWorkXenograft procedurebonechildhood sarcomachromatin isolation by RNA purification sequencingchromatin remodelingexperimental studygene repressiongenetic signaturegenome-widein vivoknock-downmembermortalitynoveloverexpressionprotein functionprotein protein interactionrare cancersarcomatranscription factortranscriptometranscriptome sequencingtumortumor growthtumor progressiontumorigenesisyoung adult
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Ewing sarcoma is a rare tumor that occurs in children and young adults. The driving oncogenic event in this
disease is most commonly the translocation EWS/FLI. Similar translocations involving ETS transcription
factors occur in other malignancies, including prostate cancer, broadening the potential relevance of our
studies. Prior work has determined that EWS/FLI can lead to chromatin reprogramming by repressing some
enhancers while activating others through direct binding. Our own data indicates that EWS/FLI also
upregulates expression of lncRNAs. The primary goal of this proposal is to elucidate the molecular function of
lncRNAs in Ewing sarcoma. Our preliminary data indicates that two lncRNAs, EWSAT1 and EWSAT2, may be
involved in the oncogenic effects of Ewing sarcoma. Knock-down of either of these RNAs strongly decreases
proliferation of Ewing tumors in vitro and in vivo. Furthermore, RNAseq analysis indicates that both of these
lncRNAs repress a significant number of genes also known to be repressed by EWS/FLI. Our primary goal in
this proposal is to elucidate the molecular function through which these lncRNAs act to promote Ewing
sarcoma. We will focus our studies on determining how these lncRNAs lead to transcriptional repression.
In Aim 1, we will elucidate define how expression of EWSAT1 and 2 alters key protein-protein interactions in
Ewing cells. Specifically, we will test the hypothesis that EWSAT1 or 2 expression alters PPIs for EWS/FLI,
EWS or hnRNPK. In Aim 2, we will test the hypothesis that EWSAT1 or 2 function by modulating the ability of
EWS/FLI to bind to specific enhancers. ChIPseq and ChIRPseq will be used to determine how these lncRNAs
interact with chromatin and how they alter binding of histones and other chromatin regulators. In Aim 3, we will
elucidate the functional consequences of EWSAT1/2 loss or overexpression using Ewing patient derived
xenografts and cell lines.
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专著(0)
科研奖励(0)
会议论文
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资助金额:$27.22万
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财政年份:2009
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资助金额:$27.0万
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财政年份:2009
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依托单位:
Research Training in Childhood Cancer
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资助金额:$35.97万
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财政年份:2007
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依托单位:
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资助金额:$31.29万
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财政年份:2007
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依托单位:
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依托单位:
Tumor progression in a mouse model of lung cancer
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资助金额:$13.58万
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财政年份:2003
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依托单位:
Tumor progression in a mouse model of lung cancer
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资助金额:$13.58万
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国内基金
海外基金
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依托单位: