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Grant Details

Grant Number: 5R01CA172460-05 Interpret this number
Primary Investigator: Chen, Jia
Organization: Icahn School Of Medicine At Mount Sinai
Project Title: Microrna & Breast Cancer: Functional Characterization in a Population-Based Study
Fiscal Year: 2017
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Abstract

DESCRIPTION (provided by applicant): Despite considerable advancement in our knowledge about the significant role of microRNA (miRNA) in fundamental cellular processes related to cancer, most data come from in vitro/animal models or population studies with limited scope. There is a critical need for systematic investigation on the role of miRNA in breast cancer in well-designed population studies that take into account the complexity of miRNA functions and multifactorial nature of breast cancer. Herein, we have designed a hypothesis-driven, technology-enabled translational project aimed at systematically elucidating the role of miRNA in breast cancer survival. Taking advantage of the latest results from the Cancer Genome Atlas (TCGA) and our improved deep sequencing method, we will validate/identify breast cancer dysregulated miRNAs in breast tumors of representative clinical subtypes. We will employ multiple in vitro assays to characterize these miRNAs for their potential in cell growth/proliferation, differentiation, and cancer cell stemness, as well as to identify their down-stream targets in breast cell lines. We will then independently validate the laboratory findings in a population-based epidemiologic study, the Long Island Breast Cancer Study Project (LIBCSP). The unique strength of the proposed study is our ability to incorporate latest genomic technology (deep sequencing), functional molecular methods (in vitro assays), in which phenotypic relevance of candidate miRNAs can be characterized, with classic epidemiology (population-based study), in which complex exogenous factors and patient information can be taken into account. This multi-scale, multi-disciplinary, and multi-directional approach allows a better characterization of the causal relationship between miRNA and breast cancer development and progression. This project has the real potential to identify a miRNA signature that predicts breast cancer outcomes.

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Publications

Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats.
Authors: Gopalakrishnan K. , Teitelbaum S.L. , Wetmur J. , Manservisi F. , Falcioni L. , Panzacchi S. , Gnudi F. , Belpoggi F. , Chen J. .
Source: Journal Of Mammary Gland Biology And Neoplasia, 2018-06-28 00:00:00.0; , .
EPub date: 2018-06-28 00:00:00.0.
PMID: 29956080
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Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis.
Authors: Aushev V.N. , Lee E. , Zhu J. , Gopalakrishnan K. , Li Q. , Teitelbaum S.L. , Wetmur J. , Degli Esposti D. , Hernandez-Vargas H. , Herceg Z. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2018-02-01 00:00:00.0; 24(3), p. 581-591.
EPub date: 2017-11-14 00:00:00.0.
PMID: 29138345
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miR-500a-5p regulates oxidative stress response genes in breast cancer and predicts cancer survival.
Authors: Degli Esposti D. , Aushev V.N. , Lee E. , Cros M.P. , Zhu J. , Herceg Z. , Chen J. , Hernandez-Vargas H. .
Source: Scientific Reports, 2017-11-21 00:00:00.0; 7(1), p. 15966.
EPub date: 2017-11-21 00:00:00.0.
PMID: 29162888
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A new method to study the change of miRNA-mRNA interactions due to environmental exposures.
Authors: Petralia F. , Aushev V.N. , Gopalakrishnan K. , Kappil M. , W Khin N. , Chen J. , Teitelbaum S.L. , Wang P. .
Source: Bioinformatics (oxford, England), 2017-07-15 00:00:00.0; 33(14), p. i199-i207.
PMID: 28881990
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Changes In Mammary Histology And Transcriptome Profiles By Low-dose Exposure To Environmental Phenols At Critical Windows Of Development
Authors: Gopalakrishnan K. , Teitelbaum S.L. , Lambertini L. , Wetmur J. , Manservisi F. , Falcioni L. , Panzacchi S. , Belpoggi F. , Chen J. .
Source: Environmental Research, 2016-10-28 00:00:00.0; 152, p. 233-243.
PMID: 27810681
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Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers.
Authors: Lee E. , Ito K. , Zhao Y. , Schadt E.E. , Irie H.Y. , Zhu J. .
Source: Bioinformatics (oxford, England), 2016-01-01 00:00:00.0; 32(1), p. 96-105.
EPub date: 2016-01-01 00:00:00.0.
PMID: 26358730
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Characterising the epigenome as a key component of the fetal exposome in evaluating in utero exposures and childhood cancer risk.
Authors: Ghantous A. , Hernandez-Vargas H. , Byrnes G. , Dwyer T. , Herceg Z. .
Source: Mutagenesis, 2015 Nov; 30(6), p. 733-42.
PMID: 25724893
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Environmental exposures in utero and microRNA.
Authors: Kappil M. , Chen J. .
Source: Current Opinion In Pediatrics, 2014 Apr; 26(2), p. 243-51.
PMID: 24632543
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