MicroRNAs in the imprinted DLK1-DIO3 region repress the epithelial-to-mesenchymal transition by targeting the TWIST1 protein signaling network.

ABSTRACT: Development of metastatic disease accounts for the vast majority of cancer-related deaths. Nevertheless, few treatments exist that are designed to specifically inhibit processes that drive tumor metastasis. The imprinted DLK1-DIO3 region contains tumor-suppressing miRNAs, but their identity and function remain indeterminate. In this study we identify seven miRNAs in the imprinted DLK1-DIO3 region that function cooperatively to repress the epithelial-to-mesenchymal transition, a critical step that drives tumor metastasis, as well as proliferation of carcinoma cells. These seven miRNAs (miRs 300, 382, 494, 495, 539, 543, and 544) repress a signaling network comprising TWIST1, BMI1, ZEB1/2, and miR-200 family miRNAs and silencing of the cluster, which occurs via hypermethylation of upstream C

SUBMITTER: Haga CL 

PROVIDER: S-EPMC3522270 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature