Role of a Novel Family of Short RNAs, tRFs, in Prostate Cancer
Abstract
Objective: Diagnosis and treatment of prostate cancer is still a challenge all around the world. We propose to study a new molecular driver of prostate cancer to ascertain its contribution to prostate cancer growth. Rationale: Prostate cancer arises from uncontrolled division of prostate epithelium cells and eventually leads to invasion and spread from one organ/part to another. Earlier studies on prostate cancer suggest the involvement of many oncogenes and tumor suppressor genes as the molecular drivers of prostate cancer. In recent years, studies have shown small RNAs such as microRNAs (miRNAs) are involved in the pathogenesis of prostate cancer. This proposal is focused on a novel set of small RNAs similar to miRNAs that are derived from transfer RNA (tRNA) called tRNA fragments (tRFs). I want to test which tRFs are misexpressed in prostate cancer, how they regulate gene expression, and whether they can be used as biomarkers and therapeutic targets. Career Goals: As a bioinformatician, new to prostate cancer, I want to be an independent investigator using bioinformatics to understand prostate cancer by analysis of genomics data of these cancers. The training plan will introduce me to prostate cancer and teach me bioinformatics techniques essential for analysis of genomic data. The research plan will direct me to the study of small RNAs in a novel new direction that I can develop further when I have my own lab. Applications: Individual tRFs elevated in prostate cancer can be used as a biomarker in tumor samples and even in blood samples from patients. Discovering targets that are altered because of changes in tRFs will demonstrate how tRFs can regulate prostate cancer. Thus, understanding the role of tRFs and their targets in prostate cancer will discover new ways of diagnosis and treatment of prostate cancer. The research is very basic, but interim outcomes will be the identification of oncogenic tRFs or tumor suppressive tRFs and the target that these tRFs regulate to have the said oncogenic or tumor suppressive effects. Another outcome will be the development of novel bioinformatics tools that can be used by other researchers to study tRFs in the context of other cancers. Contributions to Prostate Cancer Research: tRFs have not been studied in prostate cancer, although our published results clearly indicate that these RNAs associate with cellular proteins and mRNAs in a way similar to miRNAs. Thus, the major contribution will be to identify a new driver of prostate cancer. A secondary contribution will be the development of bioinformatics tools to profile tRFs in newly diagnosed prostate cancers and thereby predict the aggressiveness of the tumor.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610390
Entities
People
- Manjari Kiran
Organizations
- United States Army
- University of Virginia