Discovery and Characterization of PRCAT47: A Novel Prostate Lineage and Cancer-Specific Long Noncoding RNA
Abstract
Background: Prostate cancer is the second most common epithelial cancer and the leading cause of cancer-related death in men in the United States. It has been estimated that about 1 in 7 men will be diagnosed with prostate cancer during his lifetime. Prostate cancer, if remain localized to the site or origin, is highly treatable and hence most men diagnosed with prostate cancer do not die; however, some patients progress to an aggressive disease where the cancer spreads to multiple organs. There are tests available that can efficiently diagnose the disease; however, these tests are unable to predict whether the patient will progress to aggressive disease or not. Therefore, there is an urgent need to (1) identify patients that will progress to aggressive disease; (2) identify new and more potent drugs for patients with advanced metastatic disease; and (3) understand why cancer progresses and becomes more aggressive. Objective and Rationale: Long non-coding RNAs (lncRNA) are newly discovered class of genes that do not make any proteins but are known to play important role in cancer initiation as well as progression to lethal disease. Importantly, lncRNA expression has been shown to be limited to one particular tissue and cancer type, which makes them important biomarkers. In this proposal, we plan to investigate the role of one such lncRNA called prostate cancer associated transcript-47 (PRCAT47). PRCAT47 is present in localized and aggressive prostate cancer cells and is required for the growth of these cells. PRCAT47 also regulate another important gene, Androgen Receptor, that has been well shown to play a critical role in prostate cancer development. This proposal will utilize cutting-edge technologies and large-scale patient data to study the following aspect of PRCAT47. (1) What is the role of PRCAT47 in the formation of prostate cancer as well as progression of localized highly treatable disease to a more aggressive lethal disease? (2) Can PRCAT47 expression be used for early diagnosis of prostate cancer? (3) Can PRCAT47 levels be used to distinguish patients that will progress to aggressive disease? (4) Can we develop new therapies for aggressive prostate cancer patients using PRCAT47 as a target? Clinical Applicability: The goal of this project is to understand the role of prostate lncRNA in the progression of localized prostate cancer to more advanced metastatic disease and to explore the potential use of this lncRNA as a biomarker and therapeutic target. While the initial discoveries will be immediately useful to understand the biology of disease and to evaluate the therapeutic and biomarker potential of PRCAT47, our ultimate goal is to transform the scientific findings into clinical tools. With the support from prominent scientists in the field of prostate cancer as well as backing from industry partners, we are hopeful that we will be quickly able to translate our scientific findings into clinical treatments and prognostic tools. In summary, our proposal directly addresses several of the Prostate Cancer Research Program overarching challenges such as, distinguishing indolent from aggressive disease in men diagnosed with prostate cancer, development of better tools for early detection of clinically relevant disease and to develop effective novel treatments for men with advanced lethal disease. In addition, this project will advance the field of lncRNA biology especially by discovering the molecular basis of their biological mechanism.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610314
Entities
People
- Rohit Malik
Organizations
- United States Army
- University of Michigan