The overall hypothesis of this PPA is to identify risk assessment of certain genetic markers such as miRNAs, single nucleotide mismatch repair genes or SNPs, and X-linked genes (such as TSPX) since there is evidence that they are associated with prostate cancer. The first project is to investigate the miRNAs that may serve as markers of prostate cancer by virtue of their action in suppression of oncogenic or tumor suppressor gene expression. The studies aim at delineating the underlying mechanisms that control these processes. The second project is to investigate the role of SNPs in mismatched repair (MMR) genes in prostate cancer susceptibility and progression. The third project is to investigate involvement in prostate cancer risk of the X-linked tumor suppressor gene (TSPX) which is a tumor repressor and corepressor for AR functions for its involvement in prostate cancer risk and progression. The three projects in the PPA will be supported by three Cores: 1) Administrative Core;2) Tissue/Morphology/Molecular Core;and 3) Statistical Core. Significance: Strengths: The study of the expression of three types of molecular biomarkers of prostate cancer in a large number prostate specimens (at different stages of pathology) represents an important step towards developing a system of patient identification with respect to their potential for disease progression. This knowledge could be of much value in devising therapy approaches. This research will also contribute to the aspect of knowledge on prostate cancer pathobiology that is currently missing. Studies on the molecular mechanisms of the functions of the three types of biomarkers are also well considered and will advance the fundamental knowledge pertaining to the function of these biomarkers. A particularly noteworthy point is that investigation of molecular biomarkers along the proposed lines has not been undertaken previously making this a highly novel endeavor. The success in the proposed studies could lea

Public Health Relevance

Prostate cancer is one of the most common malignancies among our Veterans. The major problem in the management of prostate cancer is the lack of biomarkers that can identify which localized prostate tumors are likely to progress, metastasize, or become fatal, and thus require more aggressive clinical intervention. Based on the published literature, microRNAs, single nucleotide polymorphisms of mistmatch repair genes and X- linked tumor suppressor gene are associated with prostate cancer. Currently, there are no genetic biomarkers for the risk assessment of prostate cancer. Therefore, the main goal of this project is to investigate whether microRNAs, SNPs of mismatch repair genes, and X-linked genes can be utilized as a novel genetic tool for the risk assessment of prostate cancer using in vitro models. Since prostate cancer is one of the most common malignancies among our Veterans the identification of genetic biomarkers for the risk assessment of prostate cancer will have a significant impact on Veterans health and the VA mission.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Veterans Administration (IP1)
Project #
1IP1BX001604-01
Application #
8246285
Study Section
Oncology A (ONCA)
Project Start
2012-10-01
Project End
2016-09-30
Budget Start
2012-10-01
Budget End
2013-09-30
Support Year
1
Fiscal Year
2013
Total Cost
Indirect Cost
Name
Veterans Affairs Medical Center San Francisco
Department
Type
DUNS #
078763885
City
San Francisco
State
CA
Country
United States
Zip Code
94121
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Bucay, N; Sekhon, K; Yang, T et al. (2017) MicroRNA-383 located in frequently deleted chromosomal locus 8p22 regulates CD44 in prostate cancer. Oncogene 36:2667-2679
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Shiina, Marisa; Hashimoto, Yutaka; Kato, Taku et al. (2017) Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians. Oncotarget 8:8356-8368
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Bhat, Nadeem S; Colden, Melissa; Dar, Altaf A et al. (2017) MicroRNA-720 Regulates E-cadherin-?E-catenin Complex and Promotes Renal Cell Carcinoma. Mol Cancer Ther 16:2840-2848
Bucay, Nathan; Bhagirath, Divya; Sekhon, Kirandeep et al. (2017) A novel microRNA regulator of prostate cancer epithelial-mesenchymal transition. Cell Death Differ 24:1263-1274
Hashimoto, Yutaka; Shiina, Marisa; Kato, Taku et al. (2017) The role of miR-24 as a race related genetic factor in prostate cancer. Oncotarget 8:16581-16593
Bucay, Nathan; Sekhon, Kirandeep; Majid, Shahana et al. (2016) Novel tumor suppressor microRNA at frequently deleted chromosomal region 8p21 regulates epidermal growth factor receptor in prostate cancer. Oncotarget 7:70388-70403
Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot et al. (2016) Pre-clinical Orthotopic Murine Model of Human Prostate Cancer. J Vis Exp :

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