Quantitatively controlling expression of miR-17~92 determines colon tumor progression in a mouse tumor model.

ABSTRACT: The miRNA cluster miR-17~92 targets mRNAs involved in distinct pathways that either promote or inhibit tumor progression. However, the cellular and molecular mechanisms underlying miR-17~92 cluster-mediated protumorigenic or anti-tumorigenic effects have not been studied. Herein, we determined that inhibition of colon cancer progression is dictated by quantitatively controlling expression of the miR-17~92 cluster. miR-19 in the context of the miR-17~92 cluster at medium levels promoted tumor metastasis through induction of Wnt/β-catenin-mediated epithelial-mesenchymal transition by targeting to the tumor-suppressor gene, PTEN. However, higher levels of the miR-17~92 cluster switched from PTEN to oncogenes, including Ctnnb1 (β-catenin) via miR-18a, which resulted in inhibition of tumor grow

SUBMITTER: Jiang H 

PROVIDER: S-EPMC4005973 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature