Investigating the Long Noncoding RNA PLUTO-201 as a Driver and Therapeutic Target in Prostate Cancer
Abstract
Scientific Objective and Rationale: Prostate cancer is a heterogeneous disease and is still the second most common cause of cancer related deaths in men in the United States. While many prostate cancers are indolent, an important subset of patients experience disease recurrence after conventional therapy and progress to metastatic castration-resistant prostate cancer (CRPC), which is currently incurable. For these men, optimal treatment is not known. To identify the right treatment for the right patient at the right time, we need to better understand the mechanisms underlying the disease progression and to develop better therapeutic approaches directed against these disease drivers. Traditionally, protein-coding genes (genes that make RNA, which then becomes protein) have served as the foundation of cancer biology and therapeutics. However, there is increasing evidence that non-protein-coding genes (genes that make RNA but do not become proteins) can have complex biological functions of their own. Of the different types of non-protein coding genes, long non-coding RNAs (lncRNAs) in particular are emerging as an important class of molecules that drive the development and progression of prostate cancer. Our team recently performed a large sequencing study on close to 8,000 human cancer samples and performed computational approaches to discover nearly 50,000 new lncRNAs. These 50,000 new lncRNA genes represent a new area of cancer biology -- and far surpass the number of known protein-coding genes in number. Of all the newly identified lncRNAs, we have determined that one of them -- named PLUTO-201 (Prostate Locus of Uncharacterized Transcript Outlier 201) -- is most strongly associated with the development of metastases in prostate cancer, in a group of >1000 patients with prostate cancer. In these group of men, PLUTO-201 was more enriched in prostate cancers that metastasized (versus those that did not), when compared to every other known protein-coding gene or lncRNA. Thus, we hypothesize that PLUTO-201 may trigger aggressive prostate cancer and can be employed as a therapeutic target for prostate cancer treatment. Thus, this proposal aims to understand how PLUTO-201 drives prostate cancer and to develop novel therapeutic approaches for targeting PLUTO-201. Career Goals and Training Plan: My professional research training to date has centered on pharmaceutical sciences, during both my undergraduate and graduate school training. For my postdoctoral fellowship and for the remainder of my career, I have decided to focus on prostate cancer because I believe that advances in the treatment of this disease will impact the greatest number of people, both in the United States, where it is one of the most prevalent cancers, and in my birth country of China, where is unfortunately the top cancer in terms of relative increases in incidence (in men) and in mortality (across both genders) over the last decade. My long-term career goals include (1) the identification of molecular mechanisms that are involved in prostate cancer initiation and progression and (2) the development of safe and effective therapies to treat prostate cancer. I have assembled a diverse group of mentors including Dr. Felix Feng, a nationally acclaimed physician-scientist in the field of prostate cancer biology and therapeutics, Dr. Michael McManus, a renowned RNA biologist, and Dr. Peixuan Guo, a top RNA nanobiotechnology expert. All the mentors are examples of professional excellence and have strong records of mentoring trainees. I will work closely with my mentors and learn from them. In addition, the proposed studies will allow me to further develop my critical thinking approaches and to learn new skills and techniques for prostate cancer research. Additionally, the training component of this plan will allow me to engage a variety of seminars, courses, and workshops in the areas of prostate cancer therapy, cancer biology, genetics, biost
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710192
Entities
People
- Hui Li
Organizations
- United States Army
- University of California, San Francisco