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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


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.



Publications

PAM50- and immunohistochemistry-based subtypes of breast cancer and their relationship with breast cancer mortality in a population-based study.
Authors: Wang L. , Li Q. , Aushev V.N. , Neugut A.I. , Santella R.M. , Teitelbaum S. , Chen J. .
Source: Breast cancer (Tokyo, Japan), 2021 Nov; 28(6), p. 1235-1242.
EPub date: 2021-05-18.
PMID: 34003448
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Tumor expression of environmental chemical-responsive genes and breast cancer mortality.
Authors: Aushev V.N. , Gopalakrishnan K. , Teitelbaum S.L. , Parada H. , Santella R.M. , Gammon M.D. , Chen J. .
Source: Endocrine-related cancer, 2019 12; 26(12), p. 843-851.
PMID: 31593922
Related Citations

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 09; 23(3), p. 149-163.
EPub date: 2018-06-28.
PMID: 29956080
Related Citations

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; 24(3), p. 581-591.
EPub date: 2017-11-14.
PMID: 29138345
Related Citations

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; 7(1), p. 15966.
EPub date: 2017-11-21.
PMID: 29162888
Related Citations

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; 33(14), p. i199-i207.
PMID: 28881990
Related Citations

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, 2017 Jan; 152, p. 233-243.
EPub date: 2016-10-29.
PMID: 27810681
Related Citations

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; 32(1), p. 96-105.
EPub date: 2015-09-10.
PMID: 26358730
Related Citations

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.
EPub date: 2015-02-26.
PMID: 25724893
Related Citations

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
Related Citations




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