title: Merlin negative regulation by miR-146a promotes cell transformation.
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.
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
authors.forename: Erick I
authors.initials: EI
authors.lastname: Pérez-García
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
authors.forename: Karla F
authors.initials: KF
authors.lastname: Meza-Sosa
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
authors.forename: Yaxem
authors.initials: Y
authors.lastname: López-Sevilla
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
authors.forename: Nohemi
authors.initials: N
authors.lastname: Camacho-Concha
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
authors.forename: Nilda C
authors.initials: NC
authors.lastname: Sánchez
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
authors.forename: Leonor
authors.initials: L
authors.lastname: Pérez-Martínez
authors.affiliation: Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico. Electronic address: gustavo@ibt.unam.mx.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pedraza-Alva
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025581:Neurofibromin 2
chemical_list: D025581:Neurofibromin 2
keywords: Merlin; Metastasis; miR-146a; microRNAs