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 )
- 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 Goals (Katie)
Project Details and Methods (Kristin)
Detecting miRNA phenotypes is apparently difficult, according to the Weinberg paper below .
Predicted Outcomes (Kristin)
including societal impact.
Needed Resources (Kristin)
e.g., financial, cell stocks, etc
Societal Impact (Kristin)
-  "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)
-  "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.
-  "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)
-  "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)
-  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.