Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10749125 | Biochemical and Biophysical Research Communications | 2015 | 7 Pages |
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.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Erick I. Pérez-GarcÃa, Karla F. Meza-Sosa, Yaxem López-Sevilla, Nohemi Camacho-Concha, Nilda C. Sánchez, Leonor Pérez-MartÃnez, Gustavo Pedraza-Alva,