Preliminary studies show that in L1M1863 (human colon cancer) cells, miR-21 and miR-31 are upregulated during TGF-P-induced epithelial-mesenchymal transition (EMT). This proposal aims to explore the significance of miR-21 and miR-31 as effectors or modifiers of TGF-3 signaling in the context of EMT by 1) modulating the function of these miRNAs and evaluating the effect on EMT marker expression and 2) identifying mRNA targets of miR-21 and miR-31 that are relevant for EMT. The experiments.proposed here are a new angle to study cellular regulation by TGF-P and will significantly advance current understanding of how TGF-(3 regulates growth and differentiation of many types of cells. Abnormalities in TGF-(3 signaling are strongly implicated in the development of many diseases, particularly cancer. A better knowledge of cellular regulation by TGF-p is essential to understand mechanisms of cancer development, and provides vital information for the design of therapeutic interventions.
|Cottonham, Charisa L; Kaneko, Satoshi; Xu, Lan (2010) miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells. J Biol Chem 285:35293-302|