Interrogating the Mechanism of Long Noncoding RNA ARlnc-1 in Regulating AR Signaling
Abstract
Background: Prostate cancer is the second most commonly diagnosed cancer and the second leading cause of cancer death in men in the United States. Androgen, which is a hormone that influences the growth and development of the male reproductive system, plays a key role in prostate cancer development. Thus, most prostate cancer can be treated with Androgen Deprivation Therapy. However, some patients develop an aggressive disease, where the cancer comes back and may spread to multiple organs. In these patients, even though androgen is deprived, the physiological functions downstream of androgen remain activated, which explains the recurrence of disease. Therefore, there is an urgent need to: (1) Understand why these physiological functions remain activated after deprivation of androgen and how they contribute to cancer progression, and (2) Identify new target and therapeutic method to treat patients with advanced disease. Objective and Rationale: Long non-coding RNAs (lncRNA) are a class of genes that do not make any proteins. Their biological functions are diverse and largely undetermined. In cancer, they have been shown to contribute to disease progression. In this proposal, we will study an lncRNA that has a strong association with prostate cancer progression, ARlnc1. This lncRNA is interesting in that it helps to maintain the physiological functions downstream of androgen. This effect is realized through an Androgen binding partner, Androgen Receptor. Delineating the exact mechanism behind it will help us develop therapeutic strategies to interfering with physiological functions downstream of androgen in patients with advanced disease. This project will utilize cutting-edge technologies to study the following aspects about ARlnc1. (1) How does ARlnc1 regulate Androgen Receptor and its downstream physiological functions? (2) Can we use the relationship in (1) to develop novel therapeutic strategies for patient with advanced prostate cancer? Clinical Applicability: The goal of this project is to understand the functioning mechanisms of an lncRNA that associates with prostate cancer progression and to evaluate its potential use as a therapeutic target. Discoveries made here will help to explain how physiological functions downstream of androgen are sustained in advanced prostate cancer. Furthermore, if ARlnc1 is validated as a therapeutic target in our study, in future we can develop clinical treatments targeting ARlnc1 for prostate patients with advanced disease. Career Goal in Cancer Research: My long-term career goal is to conduct translational cancer research as an independent investigator while mentoring young investigators. Training at the Molecular and Cellular Pathology Program at University of Michigan has shaped this goal by offering me an exceptional laboratory experience, an interactive scientific community, and an opportunity to translate basic research into cutting-edge therapy. My mentor, Dr. Chinnaiyan, is a worldwide leader in the field of translational prostate cancer research. He will offer guidance and suggestions throughout the project and provide opportunities for me to interact with experienced cancer researchers. I will present my project at local and national meetings to receive feedback about my work from prostate cancer researchers around the world. At the end of this training process, I will develop into an investigator that can conduct translational research independently in the field of prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710134
Entities
People
- Yajia Zhang
Organizations
- United States Army
- University of Michigan