User:Cecilia Cisar/Notebook/Mod 3 Research Proposal

Project Description To design bacteria that use specific miRNA signatures to target cancer cells. Overview for this assignment and FAQ Overview MiRNAs are believed to be important in oncogenesis, as different groups of miRNAs act as either tumor suppressors or oncogenes. For example, miR-145, miR-133a and miR-133b have been found to be tumor-suppressive miRNAs that directly regulate the oncogene FSCN1. [5] Changes in miRNA expression have been detected in many types of human cancers, in a way that seems to be linked to genomic amplifications, mutations, and deletions. "MiRNA expression fingerprints correlate with clinical and biological characteristics of tumours, including tissue type, differentiation, aggression and response to therapy." [1] Some bacteria use miRNA to target and post-transcriptionally repress proteins that are involved in innate immune response, [2] and other bacteria release effectors that inhibit miRNA immune response. [3] (Conversely, some miRNA-regulated immune response pathways are activated by bacteria. [4]) Bacteria could be designed to treat various kinds of tumors based on their miRNA expression fingerprint through up/down regulation of oncogene miRNA expression. Potential Problems Immune response Cancer patients may already be immunocompromised through other treatments, so this may not be as big of an issue as it would initially seem, but this leads to... Pathogenicity If my 20.020 project taught me anything, it's that people are squeamish about introducing bacteria into things even if there isn't anything to point towards it being problematic. Would saying that there should be nothing wrong with the chassis and that it'll have to go through clinical testing be enough? Targeting of cancer cells Bacteria do not specifically target things based on miRNA signatures Could we rely on bacteria to stay localized, depending on treatment method? Would regulation of oncogenes in non-target area be an issue? I want to think it would just make cancer-causing mutations even less likely in affected areas, even if they were not cancerous in the first place... Targeting of miRNAs This is going to be what we say the focus of the research will be, right? Do we know enough to take a stab at this? It may be worth reading that third paper closer to see if they specify any sort of mechanism... References Calin, George A., and Carlo M. Croce. "MicroRNA signatures in human cancers." Nature Reviews Cancer 6.11 (2006): 857-866. Ma, Feng, et al. "The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ."Nature immunology 12.9 (2011): 861-869. Navarro, Lionel, et al. "Suppression of the microRNA pathway by bacterial effector proteins." Science 321.5891 (2008): 964-967. Taganov, Konstantin D., et al. "NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses." Proceedings of the National Academy of Sciences 103.33 (2006): 12481-12486. Kano, M., Seki, N., Kikkawa, N., Fujimura, L., Hoshino, I., Akutsu, Y., Chiyomaru, T., Enokida, H., Nakagawa, M. and Matsubara, H. (2010), miR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int. J. Cancer, 127: 2804–2814.

Recently Edited Notebook Pages 2017-09-26 23:56:17 User:Cecilia Cisar/Notebook/Mod 3 Research Proposal/Entry Base