title: miR-142-3p Is a Regulator of the TGFβ-Mediated Vascular Smooth Muscle Cell Phenotype.
abstract: The transforming growth factor β (TGFβ) signaling pathway is critical for the promotion and maintenance of the contractile phenotype of vascular smooth muscle cells (VSMCs). Though multiple microRNAs (miRNAs) implicated in the regulation of the VSMC phenotype have been identified, the modulation of miRNAs in the VSMCs by TGFβ signaling has not been fully described. In this study, we identified microRNA-142-3p (miR-142-3p) as a modulator of the VSMC phenotype in response to TGFβ signaling. We show that miR-142-3p is induced upon TGFβ signaling, leading to the repression of a novel target, dedicator of cytokinesis 6 (DOCK6). The downregulation of DOCK6 by miR-142-3p is critical for cell migration. Thus, this study demonstrates that miR-142-3p is a key regulator of the TGFβ-mediated contractile phenotype of VSMCs that acts through inhibiting cell migration through targeting DOCK6.
authors.affiliation: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Republic of Korea.
authors.forename: Kwangho
authors.initials: K
authors.lastname: Kim
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Dong Kwon
authors.initials: DK
authors.lastname: Yang
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 701-310, Republic of Korea.
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Republic of Korea.
authors.forename: Hara
authors.initials: H
authors.lastname: Kang
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010641:Phenotype; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism
chemical_list: C000607938:DOCK6 protein, human; D020662:Guanine Nucleotide Exchange Factors; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta
keywords: DOCK6; MICRORNA-142-3p; TGFβ; VASCULAR SMOOTH MUSCLE CELLS