MiRNA profiling of tumor-derived exosomes.

摘要

Cancers and infectious diseases are becoming a growing public health problem in the world today. The importance of my work for public health is in detecting these diseases earlier and more accurately, potentially leading to better therapies and higher survival rates for patients. Current diagnostic techniques focus on detecting antibodies from serum, gene expression and miRNA profiles of tumor tissues and, more recently, in the bodily fluids of patients.;This dissertation shows a novel technique that makes use of small microvesicles called exosomes and the microRNAs (miRNAs) they carry for the potential diagnosis of cancer. Exosomes are small (40-100 nm) membrane-bound vesicles that are created from the inverse budding of the multivesicular endosome and originate from a variety of tumor types. Exosomes can be easily purified from cell cultures and serum of patients and have recently been shown to carry small non-coding RNAs called miRNAs. In the first part of this study, I developed techniques that enabled us to increase the amount of our exosome and total RNA starting material before proceeding to use these as potential diagnostics for head and neck cancers.;Although the use of exosomes to diagnose diseases is not novel, the use of miRNAs present in tumor-derived exosomes is a new approach. In the final two chapters, I discuss the use of exosomes to diagnose KSHV viral infections as well as head and neck cancer. Increasing the accuracy and reducing the amount of starting material needed for these studies would provide a non-invasive technique to detect viral infections and cancers. This would help in providing earlier therapeutic treatments and help to increase the longevity and quality of life of patients.