Pérez-García Erick I, Meza-Sosa Karla F, López-Sevilla Yaxem, Camacho-Concha Nohemi, Sánchez Nilda C, Pérez-Martínez Leonor, Pedraza-Alva Gustavo
Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62210, Mexico.
Biochem Biophys Res Commun. 2015 Dec 25;468(4):594-600. doi: 10.1016/j.bbrc.2015.10.156. Epub 2015 Nov 5.
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.
通过有害突变或经由持续生长因子受体信号介导的机制进行蛋白质降解，导致肿瘤抑制因子Merlin失活，会引发细胞转化和肿瘤发展。除了这些机制外，我们在此表明，miRNA依赖的Merlin蛋白水平负调控也会促进细胞转化。我们提供的实验证据表明，miR-146a通过与NF2 mRNA 3´非翻译区的一个进化保守序列相互作用，负调控Merlin蛋白水平。miR-146a在A549肺上皮细胞中下调Merlin会导致细胞增殖、迁移和组织侵袭增强。因此，稳定转染miR-146a的细胞在体内形成了具有转移能力的肿瘤。我们的结果共同揭示了miRNA是控制Merlin肿瘤抑制功能的另一种负向机制。
