Name(s): Connie Liu High School(s): Cherry Creek High School, Greenwood Village , CO

1. Name(s): Connie Liu High School(s): Cherry Creek High School, Greenwood Village , CO Mentor: Dr. Jennifer Richer Project Title: Therapeutic Use of microRNA-200c to Treat Ovarian Cancer MicroRNAs (miRNAs), previously thought to be “junk-DNA,” are now known to be key regulators in important processes including cell proliferation and apoptosis. Particularly, miR-200c is highly expressed in normal epithelial cells but lost in aggressive ovarian cancer cells (HEY). MiR-200c was restored to HEY cells to determine how the cells changed. Results from modified wound-healing and clonogenic assays provided evidence that miR-200c-transfected cells were less migratory and more sensitive to paclitaxel. They behaved more epithelial-like than cancerous. An alternative explanation for cell adhesion and the specific mechanism behind the increased chemosensitivity previously observed was proposed and investigated. Class-III-beta-tubulin (TUBB3) is over-expressed in certain cancers resistant to microtubule-targeting, chemotherapeutic agents like paclitaxel. TUBB3 is a known target of miR-200c. While HEY cells expressing endogenous TUBB3 became more sensitive to paclitaxel, those expressing TUBB3 without its 3’UTR that contains the miR-200c binding site remained chemoresistant. Adhesion assays showed that miR-200c-transfected HEYs did not adhere as strongly to collagen IV, fibronectin, and vitronectin as non-transfected controls. Understanding how miR-200c works in normal epithelial cells and how it affects aggressive cancer cells will help us discover novel ways to treat ovarian cancer or reverse resistance and enhance the effectiveness of existing methods.