title: MicroRNA-10b Induces Vascular Muscle Cell Proliferation Through Akt Pathway by Targeting TIP30.
abstract: Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes significantly to the pathogenesis of atherosclerosis. MiR-10b has recently emerged as a critical mediator in regulating cell proliferation in many diseases. In our study, miR-10b expression was up-regulated in VSMCs isolated from atherosclerotic plaques, as well as in PDGFstimulated VSMCs.Overexpression of miR-10b promoted cell proliferation of VSMCs. Furthermore, we identified the Tat-interacting protein 30 (TIP30) as a direct target gene of miR-10b. TIP30 was down-regulated in VSMCs isolated from atherosclerosis plaques, as well as in proliferative VSMCs. Knockdown of TIP30 promoted VSMCs proliferation. In addition, miR-10b induced TIP30 down-regulation was accompanied by increased Akt phosphorylation. Akt was critical for miR-10b-mediated VSMCs proliferation. Our results demonstrated that miR-10b contributed to abnormal VSMCs proliferation through inhibiting the Akt pathway by targeting TIP30 in atherosclerosis. The modulation of miR-10b in VSMCs provides a potential target for the therapy of atherosclerosis.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. kleeo@163.com.
authors.forename: William Ka Kei
authors.initials: WK
authors.lastname: Wu
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010766:Phosphorylation / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D000123:Acetyltransferases; C111246:HTATIP2 protein, human; D051057:Proto-Oncogene Proteins c-akt