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.

Public Health Relevance

We have designed a hypothesis-driven, technology-enabled translational project aimed at systematically elucidating the role of microRNA in breast cancer survival. We will achieve this by combining deep sequencing technology, in vitro functional assays, and classic epidemiology. Knowledge gained from this study may facilitate identification of breast cancer prognostic markers, and lead to the potential development of novel chemopreventive or even therapeutic strategies against breast cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Divi, Rao L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Public Health & Prev Medicine
Schools of Medicine
New York
United States
Zip Code
Gopalakrishnan, Kalpana; Teitelbaum, Susan L; Wetmur, James et al. (2018) Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats. J Mammary Gland Biol Neoplasia 23:149-163
Aushev, Vasily N; Lee, Eunjee; Zhu, Jun et al. (2018) Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis. Clin Cancer Res 24:581-591
Petralia, Francesca; Aushev, Vasily N; Gopalakrishnan, Kalpana et al. (2017) A new method to study the change of miRNA-mRNA interactions due to environmental exposures. Bioinformatics 33:i199-i207
Gopalakrishnan, Kalpana; Teitelbaum, Susan L; Lambertini, Luca et al. (2017) Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development. Environ Res 152:233-243
Degli Esposti, Davide; Aushev, Vasily N; Lee, Eunjee et al. (2017) miR-500a-5p regulates oxidative stress response genes in breast cancer and predicts cancer survival. Sci Rep 7:15966
Lee, Eunjee; Ito, Koichi; Zhao, Yong et al. (2016) Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers. Bioinformatics 32:96-105
Ghantous, Akram; Hernandez-Vargas, Hector; Byrnes, Graham et al. (2015) Characterising the epigenome as a key component of the fetal exposome in evaluating in utero exposures and childhood cancer risk. Mutagenesis 30:733-42
Kappil, Maya; Chen, Jia (2014) Environmental exposures in utero and microRNA. Curr Opin Pediatr 26:243-51