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  • Title: Merlin negative regulation by miR-146a promotes cell transformation.
    Author: Pérez-García EI, Meza-Sosa KF, López-Sevilla Y, Camacho-Concha N, Sánchez NC, Pérez-Martínez L, Pedraza-Alva G.
    Journal: Biochem Biophys Res Commun; 2015 Dec 25; 468(4):594-600. PubMed ID: 26549232.
    Abstract:
    Inactivation of the tumor suppressor Merlin, by deleterious mutations or by protein degradation via sustained growth factor receptor signaling-mediated mechanisms, results in cell transformation and tumor development. In addition to these mechanisms, here we show that, miRNA-dependent negative regulation of Merlin protein levels also promotes cell transformation. We provide experimental evidences showing that miR-146a negatively regulates Merlin protein levels through its interaction with an evolutionary conserved sequence in the 3´ untranslated region of the NF2 mRNA. Merlin downregulation by miR-146a in A549 lung epithelial cells resulted in enhanced cell proliferation, migration and tissue invasion. Accordingly, stable miR-146a-transfectant cells formed tumors with metastatic capacity in vivo. Together our results uncover miRNAs as yet another negative mechanism controlling Merlin tumor suppressor functions.
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