title: MicroRNA-223-3p inhibits the angiogenesis of ischemic cardiac microvascular endothelial cells via affecting RPS6KB1/hif-1a signal pathway.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in the angiogenesis and cardiovascular diseases; however, the details of miRNAs regulating mechanism of angiogenesis of ischemic cardiac microvascular endothelial cells (CMECs) are not yet reported.
  
  
  RESULTS
  This study analyzes the changes of the dynamic expression of miRNAs during the process of angiogenesis of ischemic CMECs by applying miRNA chip and real-time PCR for the first time. Compared with normal CMECs, ischemic CMECs have a specific miRNAs expression profile, in which mir-223-3p has the most significant up-regulation, especially during the process of migration and proliferation, while the up-regulation is the most significant during migration, reaching 11.02 times. Rps6kb1 is identified as a potential direct and functional target of mir-223-3p by applying bioinformatic prediction, real-time PCR and Western blot. Pathway analysis report indicates Rps6kb1 regulates the angiogenesis by participating into hif-1a signal pathway. Further analysis reveals that both the gene and protein expression of the downstream molecules VEGF, MAPK, PI3K and Akt of Rps6kb1/hif-1a signal pathway decrease significantly during the process of migration and proliferation in the ischemic CMECs. Therefore, it is confirmed that mir-223-3p inhibits the angiogenesis of CMECs, at least partly, via intervening RPS6KB1/hif-1a signal pathway and affecting the process of migration and proliferation.
  
  
  CONCLUSIONS
  This study elucidates the miRNA regulating law in the angiogenesis of CMECs; mir-223-3p inhibits the process of migration and proliferation of ischemic CMECs probably via affecting RPS6KB1/hif-1a signal pathway, which in turn suppresses the angiogenesis. It is highly possible that mir-223-3p becomes a novel intervention core target in the treatment of angiogenesis of ischemic heart diseases.
authors.affiliation: Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Dai
authors.affiliation: Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Pei-Ze
authors.initials: PZ
authors.lastname: Ma
authors.affiliation: Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Song
authors.affiliation: Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D012333:RNA, Messenger; D019893:Ribosomal Protein S6 Kinases