The role of microRNA in cancer

Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Micro ribonucleic acids (miRNAs) are pivotal post-transcriptional regulators of gene expression and if research continues to reveal positive results, they will soon be used as therapeutic targets in the clinical setting for the treatment of a variety of cancers. They are evolutionarily conserved small noncoding RNAs that range from 18 to 24 nucleotides in length. There are over 1,400 miRNAs for which abundant evidence has demonstrated fundamental importance in normal cell development and up- or downregulation when they become deregulated. The deregulation of miRNAs, which can function as tumor suppressors or oncogenes, contributes to the development of cancer, among other diseases. Deregulation of tumor suppressor miRNA can occur in many different tissues of the body and lead to a variety of cancers. Tumor suppressor let-7 negatively regulates expression of an oncogenic mRNA named RAS. In lung cancer, a decrease in let-7 produces an increase in expression of RAS, which contributes to cell proliferation and tumorigenesis. In chronic lymphocytic leukemia, Bcl2 protein becomes overexpressed due to the down-regulation of tumor suppressors miRNA-15 and miRNA-16. MicroRNA-34 plays an important role in neuroblastoma in which its expression is decreased due to mutations that decrease a tumor suppressor protein, p53. Upon deregulation of oncogenic miRNAs, tumor suppressor mRNA expression is decreased and leads to multiple types of cancer. Up-regulation of the miRNA-17-92 cluster in lung cancer leads to increased cell proliferation and contributes to angiogenesis in many cancers. In B cell lymphoma, miRNA-155 becomes up-regulated along with an RNA named BIC. This up-regulation accelerates pathogenesis and up-regulation of an oncogenic protein, c-myc. MicroRNA-21 acts as an anti-apoptotic factor by downregulating apoptosis-related genes and contributing to the development of human glioblastoma. This review summarizes the present understanding of how miRNAs function at the molecular level in the body, how their deregulation contributes to tumor formation, maintenance and metastasis and how they can be used for cancer diagnosis, prognosis and therapy. With the mass amounts of knowledge gained from the current research done on miRNAs, a cancer cure may soon be developed based on the targeting of specific miRNAs. The promise of miRNAs in cancer therapeutics will depend on the development of proper delivery strategies of miRNA mimics and inhibitors, in addition to evaluation of safe usage and toxicity of therapeutic dosages.2031-01-0