Identifying a network of microRNAs and genes that regulate breast tumor metastasi
识别调节乳腺肿瘤转移的 microRNA 和基因网络
基本信息
- 批准号:8773677
- 负责人:
- 金额:$ 24.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-02-01 至 2017-01-31
- 项目状态:已结题
- 来源:
- 关键词:AlgorithmsBRCA1 geneBiological AssayBiological MarkersBiomedical EngineeringBlood CirculationBreastBreast Cancer CellBreast Cancer ModelBypassCancer PatientCancer cell lineCause of DeathCell physiologyCellsChemistryChicagoChromatinClinicalClinical MedicineCorrelation StudiesDataDetectionDrug CompoundingDrug resistanceEZH2 geneElectrophoretic Mobility Shift AssayEpithelialFamilyFatty acid glycerol estersFutureGene TargetingGenesGeneticGoalsHumanIn VitroKnowledgeLengthLentivirus VectorLuciferasesLungMalignant NeoplasmsMammary NeoplasmsMammary glandMedicineMentorsMesenchymalMessenger RNAMicroRNAsMicroarray AnalysisModelingMolecularMonitorMusMutationNeoplasm MetastasisNucleotidesOptical reporterPatientsPhasePropertyProtocols documentationRegulationReportingResearch PersonnelResearch TrainingResistanceSmall RNASpecimenStem cellsTechnologyTherapeuticToxic effectTranscriptional RegulationTranslatingTransplantationTumor-DerivedUnited StatesUniversitiesWestern BlottingXenograft Modelabstractingbasebioluminescence imagingbreast cancer diagnosiscancer cellcancer initiationcancer therapyclinical applicationimprovedin vivoinnovationlymph nodesmalignant breast neoplasmmortalityneoplastic cellnon-invasive imagingnoveloverexpressionpost-doctoral trainingpre-clinicalpreclinical studypreventpromotertherapeutic targettranscription factortumortumor growthtumor initiationtumor progression
项目摘要
Proposal: Identifying a network of miRNAs and genes that regulate breast tumor metastasis
Abstract
Metastasis is the major cause of death in breast cancer patients. However, the molecular mechanisms
underlying tumor initiation and metastasis are not clear. We have recently identified tumor initiation cells (TICs)
from human breast tumors 1,2. TICs carry certain properties of stem cells, are more resistant to conventional
cancer therapies, and are involved in tumor metastasis. How to effectively target TICs or metastasis initiating
cells (MICs) thus becomes one of the most propelling questions. Endogenous single strand small RNAs of 20-
22 nucleotides in length, known as microRNAs (miRNAs, miRs), have emerged to be powerful regulators of
tumor progression 3-15. In this project, we aim to characterize novel miRs that regulate human breast cancer
initiation and metastasis and identify their target genes. Then in our future endeavors, we will examine miR
regulation mechanisms at the transcriptional level and further translate our understanding to clinical
applications, such as novel cancer biomarkers or therapeutics.
Most previous metastasis models are limited in their ability to fully represent human tumors, due to genetic
changes accumulated in culture for human cancer cell lines, genetic differences in mouse tumor models
compared to human tumors, and bypassing the natural steps of metastasis via bloodstream inoculations. This
project will take advantage of our recently established human-in-mouse breast cancer models, which are
derived from clinical tumor specimens and develop spontaneous lung or lymph node metastases upon
orthotopic transplantation into mouse mammary fat pads. To closely monitor breast tumor initiation and
metastasis in vivo, we have also transduced primary cancer cells with optical reporters and improved the
detection sensitivity to 10 cells in vivo via non-invasive bioluminescence imaging. MiRs are more stable and
resistant to analysis protocols than mRNAs, thus serving as promising novel cancer biomarkers. Furthermore,
they are endogenous small RNAs with little toxicity compared to compound drugs; therefore hold the promise
to be developed as innovative cancer therapeutics.
Our long-term goal is to combine our understanding of tumor initiation and metastasis with knowledge in multi-
disciplinary technology (such as chemistry and bioengineering) to improve clinical medicine and reduce cancer
mortality.
Transcription
Factors
In vivo
Tumor initiation
metastasis
Future 1
Novel miRNAs
1
Future 2
In vitro
Tumor growth
Cell invasion
Target Differentiation
Genes Drug-resistance
Preclinical
Biomarkers
Therapeutics
2
A schematic figure of aims: (1) to characterize and validate miRNA candidate functions, (2) to
identify miRNA targets and their importance in BTICs and metastasis, (Future 1) transcriptional
regulation of miRNAs by transcriptional factors, and (Future 2) preclinical studies of miRNAs
and genes serving as novel biomarkers and/or therapeutic targets for breast cancer.
建议:确定调节乳腺肿瘤转移的mirna和基因网络
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
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{{ truncateString('Huiping Liu', 18)}}的其他基金
A streamlined platform for phosphoproteome mapping of human tissues
人体组织磷酸化蛋白质组图谱的简化平台
- 批准号:
10687348 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Molecular mechanisms underlying circulating tumor cell aggregation
循环肿瘤细胞聚集的分子机制
- 批准号:
10608941 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Molecular mechanisms underlying circulating tumor cell aggregation
循环肿瘤细胞聚集的分子机制
- 批准号:
10524188 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Molecular mechanisms underlying circulating tumor cell aggregation
循环肿瘤细胞聚集的分子机制
- 批准号:
9981196 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
A streamlined platform for phosphoproteome mapping of human tissues
人体组织磷酸化蛋白质组图谱的简化平台
- 批准号:
10118709 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
A streamlined platform for phosphoproteome mapping of human tissues
人体组织磷酸化蛋白质组图谱的简化平台
- 批准号:
10707474 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Molecular mechanisms underlying circulating tumor cell aggregation
循环肿瘤细胞聚集的分子机制
- 批准号:
10372102 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
A streamlined platform for phosphoproteome mapping of human tissues
人体组织磷酸化蛋白质组图谱的简化平台
- 批准号:
10259780 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Identifying a network of microRNAs and genes that regulate breast tumor metastasi
识别调节乳腺肿瘤转移的 microRNA 和基因网络
- 批准号:
8793765 - 财政年份:2014
- 资助金额:
$ 24.15万 - 项目类别:
Identifying a network of microRNAs and genes that regulate breast tumor metastasis
识别调节乳腺肿瘤转移的 microRNA 和基因网络
- 批准号:
9459147 - 财政年份:2014
- 资助金额:
$ 24.15万 - 项目类别:
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