The Regulatory Axis of lncRNA PRCAT71-AR in Advanced Prostate Cancer
Abstract
Scientific Objective: Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related death among American men. The current primary treatment for advanced prostate cancer is hormone deprivation therapy, which eventually becomes castration-resistant prostate cancer with no effective treatment options, highlighting the urgent need to identify and develop better therapeutics to target advanced prostate cancer. This proposal will provide critical insights into prostate cancer progression and identify new effective therapeutic methods for patients with castration-resistant prostate cancer. Long non-coding RNAs (lncRNAs) are a class of ribonucleic acids with 200 nucleotides longer in size that could not be translated to proteins, and they have been shown to play important roles in cancer development and progression. Detection of oncogenic lncRNAs in serum or urine could facilitate early cancer detection, and some lncRNAs could be diagnostic, prognostic, and therapeutic targets for prostate cancer. Androgen receptor (AR) has a critical role in all stages of prostate cancer; thus, identifying new molecular mechanisms underlying aberrant AR activation by lncRNAs holds great promise to improve the treatment of castration-resistant prostate cancer. As the principal investigator, I have identified an lncRNA, named PRCAT71 that is specifically expressed in prostate cancer tissues, and suppressing the expression of PRCAT71 could inhibit prostate cancer cell growth and invasiveness. Our data suggested that PRCAT71 could regulate AR expression and thus promote prostate cancer progression. This proposal will elucidate the mechanisms by which PRCAT71 promotes prostate cancer progression and metastasis and will provide potential new therapeutic targets for treating patients with castration-resistant prostate cancer. Applicability of Research: First, successful completion of the proposed studies will provide two immediate important clinical applications. This study will identify whether lncRNA PRCAT71 can be utilized as diagnostic and prognostic markers for prostate cancer by analyzing large-scale transcriptomic data from patients with prostate cancer. Second, the results of this study will identify lncRNA PRCAT71 as a promising new therapeutic target for patients with prostate cancer, particularly targeting PRCAT71 through antisense oligo to eradicate prostate cancer growth and metastasis. Ultimately, the preclinical data obtained from this proposal will provide rational to initiate new clinical trials of targeting PRCAT71 through antisense oligo to reduce prostate cancer growth and metastasis on patients with castration-resistant prostate cancer. Contributions to Prostate Cancer Research: This proposal is highly innovative. It describes a novel positive-feedback regulation mechanism between lncRNA PRCAT71 and AR, of which both PRCAT71 and AR cooperatively promote prostate cancer progression by enhancing the AR signaling pathway. The findings will greatly enhance the understanding of prostate cancer progression. Furthermore, the proposed work will identify a new effective therapeutic target for patients with advanced prostate cancer. Career Goal: My ultimate career goal is to become an independent translational prostate cancer researcher to identify and develop better mechanisms to target advanced prostate cancer by collaborating with clinicians. I obtained my doctoral degree from the laboratory of Dr. Chengchao Shou at Peking University Cancer Hospital and Institute, where I investigated the mechanisms of Phosphatase of Regenerating Liver 3 (PRL-3)-induced genome instability in colorectal cancer. To continue my training for cancer research and identify new therapeutic targets for advanced prostate cancer, I joined Dr. Qi Cao’s laboratory at Northwestern University Feinberg School of Medicine. Dr. Cao is an excellent example of a translational prostate cancer researcher with num
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110146
Entities
People
- Yongyong Yang
Organizations
- Northwestern University
- United States Army