Role of Noncoding Small RNAs in Colorectal Cancer Progression
Abstract
Colorectal cancer is the third most common type of cancer in the United States and the second leading cause of cancer-related death among men and women combined. Major risk factors for the development of colorectal cancer are a genetic predisposition, the presence of inflammatory bowel disease, and older age. Additional risk factors include environmental exposures such as ionizing radiation, which has affected “Atomic Veterans” and military involved in nuclear weapons testing. However, of increasing concern is the sharp rise in incidence of colorectal cancer in younger adults aged 20-54 that is likely related to an environmental cause. Thus, there is a clear need for better detection methods and for a better understanding of factors involved in colon cancer development and progression. Recent data suggest that certain fragments of ribonucleic acid (RNA), which are normally found in the cell and are used as a template to make proteins that are important for cellular function, are circulating in the blood of colorectal cancer patients at much higher levels compared to that of normal, healthy patients. However, how this occurs and whether these circulating small RNA fragments have any impact on cancer development or growth remains unknown. In addition, whether these RNA fragments can be used in conjunction with stool-based screening tests to identify patients with colorectal cancer remains to be fully investigated. Using mouse models of colon cancer, we have identified a small RNA fragment is increased in abundance in mice with premalignant tumors, making it an attractive measurable blood marker that can be used to identify patients at risk for developing colon cancer. In addition, our data suggest that this RNA fragment can also affect immune cell responses and promote the growth of colon cancers, making it not only a potential predictor of colorectal cancer development, but also a novel target for the treatment of colorectal cancer. The aims of this study are to test our idea that a certain small RNA fragment can modulate immune responses to promote cancer growth and to better understand the mechanism by which these fragments appear at higher levels in the circulation in the presence of colon cancer. The long-term goal of these studies is to develop small RNA signatures as potential biomarkers of colon cancer and to develop strategies targeting these small RNAs as a novel immunotherapy approach for the treatment of colorectal cancers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810407
Entities
People
- Grace Chen
Organizations
- United States Army
- University of Michigan