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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA172460-01A1
Application #
8630725
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Divi, Rao L
Project Start
2013-09-30
Project End
2018-08-31
Budget Start
2013-09-30
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$629,702
Indirect Cost
$247,253
Name
Icahn School of Medicine at Mount Sinai
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Kappil, Maya; Chen, Jia (2014) Environmental exposures in utero and microRNA. Curr Opin Pediatr 26:243-51