WFPink Proposal

Katie Thomas and Kristin Kuhn

Using MicroRNAs to treat cancer

(Optionally including a way to deliver microRNAs specifically to cancer cells)

Project Overview (Katie)

MicroRNAs are an up-and-coming field of biology; recent research has shown that they have a critical role in many types of cancers, both as oncogenes and as tumor-suppressors. Most of this research, however, has been focused towards inhibiting oncogenic miRNA activity. We propose to investigate using miRNAs (Agi: or synthethic siRNAs? can't control miRNAs) to suppress specific, known oncogenic genes.

Background Info (Katie)

• "expression level of microRNAs are altered in most human cancers"
• MicroRNAs are small non-coding RNA that regulate gene expression by inhibiting gene expression post-tranlationally.
• miRNAs are pleiotropic, meaning just one miRNA can influence many phenotypic traits.
• Changing just one base pair in a target sequence can affect the binding of miRNA. (p1)
• Certain miRNAs can refer resistance to chemotherapeutic drugs by targeting cell cycle inhibitors and down-regulating them. (p1)
• "Virtually all examined tumor types are characterized by globally abnormal miRNA expression patterns." (p2)

Research Problem (Katie)

• Investigate using miRNAs to knock out genes (like p53) that are known to cause cancer.
• Or, investigate how to regulate over-active miRNAs that cause cancers themselves. (Currently a focus of much research, according to [2])
• Or, investigate how miRNAs work by knocking out known miRNA sequences and seeing what happens. Maybe mutating them? Can we change their specificity? (Agi: Specifically what would we try to add to what is already known?)

Project Details and Methods (Kristin)

Detecting miRNA phenotypes is apparently difficult, according to the Weinberg paper below [4].

Predicted Outcomes (Kristin)

including societal impact.

Needed Resources (Kristin)

e.g., financial, cell stocks, etc

(Possible) Sources

• [1] "Paper 1": ERα-negative and triple negative breast cancer: Molecular features and potential therapeutic approaches (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T23-4WHFD55-1&_user=501045&_coverDate=12%2F31%2F2009&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000022659&_version=1&_urlVersion=0&_userid=501045&md5=59d0f4727e262100e250780b97e3126f)
• [2] "Paper 2": Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSN-4WH1GC7-C&_user=501045&_coverDate=06%2F12%2F2009&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000022659&_version=1&_urlVersion=0&_userid=501045&md5=1aa432d2843456eb7375e492ce6c2605). This paper is about using miRNAs as a generic cancer therapy - i.e., using miRNAs that don't necessarily target the affected gene.
• [3] "That Review Article We Can't Get Yet": MicroRNAs in Cancer: Small Molecules with a Big Impact (http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.24.0317v1)
• [4] "Other Review Article We Can't Get": Assaying microRNA loss-of-function phenotypes in mammalian cells: Emerging tools and their potential therapeutic utility (http://www.landesbioscience.com/journals/rnabiology/article/10081)
• [5] A possibility if we go the breast cancer route: A.J. Lowery, et al. MicroRNA signatures predict estrogen receptor, progesterone receptor and HEr2/neu receptor status in breast cancer, Breast Cancer Res. 11 (2009) R27.