MicroRNA miR-509 Regulates ERK1/2, the Vimentin Network, and Focal Adhesions by Targeting Plk1

• Published in: Scientific reports Vol. 8; no. 1; pp. 12635 - 13
• Main Authors: Liao, Guoning, Wang, Ruping, Rezey, Alyssa C., Gerlach, Brennan D., Tang, Dale D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.08.2018; Nature Publishing Group
• Subjects: 13/1; 13/51; 13/89; 13/95; 14; 14/19; 3' Untranslated Regions; 38; 38/89; 38/90; 631/443; 631/80; Adhesion; Cancer; Cell adhesion & migration; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell growth; Cell migration; Cell Movement - physiology; Cell proliferation; Cell Proliferation - physiology; Cytokinesis; Cytoskeleton; Extracellular signal-regulated kinase; Filaments; Focal Adhesions - genetics; Focal Adhesions - metabolism; Focal Adhesions - physiology; Humanities and Social Sciences; Humans; Kinases; MAP Kinase Signaling System; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Mitogen-Activated Protein Kinases - metabolism; Mitosis; multidisciplinary; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - physiology; Paxillin; Phosphorylation; Platelet-derived growth factor; Plk1 protein; Polo-like kinase; Polo-Like Kinase 1; Primary Cell Culture; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein-tyrosine kinase; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Respiratory tract; RNA-mediated interference; Science; Science (multidisciplinary); Signal Transduction; Smooth muscle; Vimentin; Vimentin - genetics; Vimentin - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-30895-8

Polo-like kinase 1 (Plk1) has been implicated in mitosis, cytokinesis, and proliferation. The mechanisms that regulate Plk1 expression remain to be elucidated. It is reported that miR-100 targets Plk1 in certain cancer cells. Here, treatment with miR-100 did not affect Plk1 protein expression in human airway smooth muscle cells. In contrast, treatment with miR-509 inhibited the expression of Plk1 in airway smooth muscle cells. Exposure to miR-509 inhibitor enhanced Plk1 expression in cells. Introduction of miR-509 reduced luciferase activity of a Plk1 3′UTR reporter. Mutation of miR-509 targeting sequence in Plk1 3′UTR resisted the reduction of the luciferase activity. Furthermore, miR-509 inhibited the PDGF-induced phosphorylation of MEK1/2 and ERK1/2, and cell proliferation without affecting the expression of c-Abl, a tyrosine kinase implicated in cell proliferation. Moreover, we unexpectedly found that vimentin filaments contacted paxillin-positive focal adhesions. miR-509 exposure inhibited vimentin phosphorylation at Ser-56, vimentin network reorganization, focal adhesion formation, and cell migration. The effects of miR-509 on ERK1/2 and vimentin were diminished in RNAi-resistant Plk1 expressing cells treated with miR-509. Taken together, these findings unveil previously unknown mechanisms that miR-509 regulates ERK1/2 and proliferation by targeting Plk1. miR-509 controls vimentin cytoskeleton reorganization, focal adhesion assembly, and cell migration through Plk1.