In the last two decades since the discovery of the first microRNA, these short, non-coding molecules have become attractive tools and targets for novel therapeutics against many diseases including cancer.
We have identified multiple TGFβ-mediated microRNAs, for example miR-181, miR-584 and miR-30, that regulate tumor suppression and progression. We efficiently reduced primary tumor growth in vivo when modulating expression of these miRNAs in preclinical orthotopic breast cancer models. We are investigating their clinical prognostic and therapeutic values in different models of solid tumors (breast, pancreatic, prostate, melanoma, liver and ovarian cancers).
Using a cutting-edge approach consisting of a pooled in vivo genome-wide CRISPR/Cas9 knockout screen in a triple negative breast cancer model, we simultaneously interrogated the oncogenic potential of all genes and microRNAs in the cell. This allowed us to identify multiple novel microRNAs with tumor suppressor and tumor promoter activities. We are currently determining how these microRNAs work to respectively prevent or promote cancer from growing and spreading, in an effort to better exploit the therapeutic potential of modulating these microRNAs to ultimately reduce tumor burden. Our lab is also looking to perform this screen in other models of breast cancer subtypes, and other models of solid tumors.
Our investigation into tumor suppressive and oncogenic microRNAs can ultimately lead to the development of targeted microRNA therapies against advanced-stage breast cancer, such as triple negative breast cancer, for which no targeted treatment exists.