title: MiR-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1.
abstract: BACKGROUND
  Airway smooth muscle cells (ASMCs) play important physiological roles in the lung, and their abnormal proliferation directly contributes to airway remodeling during development of lung diseases such as asthma. MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation, but little is known about the precise role of microRNAs in the proliferation of ASMCs.
  
  
  METHODS
  In this study, human ASMCs from asthmatic and non-asthmatic donors were used. MicroRNA and mRNA expression were measured by quantitative real-time PCR. Dual-luciferase reporter assays were performed to determine whether microRNA-138 (miR-138) binds directly to 3-phosphoinositide-dependent protein kinase-1(PDK1) 3' untranslated region (3'-UTR) to alter gene expression.
  
  
  RESULTS
  The results showed that overexpression of miR-138 reduced proliferation of human ASMCs, whereas inhibition of miR-138 increased proliferation of ASMCs. MiR-138 directly suppressed PDK1 expression by targeting the 3'-UTR of the gene. MiR-138 controls ASMC proliferation through directly inhibiting the phosphoinositide 3-kinase (PI3K) pathway.
  
  
  CONCLUSIONS
  Our study indicated that miR-138 regulation of PI3K signaling in ASMCs by altering the expression of PDK1 can have a profound impact on cell proliferation.
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: b 2 Department of Gastroenterology Medicine , Xi'an Beifang Hospital , Xi'an, Shaanxi, China.
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Yang
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Sun
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xie
authors.affiliation: a 1 Department of Respiratory Medicine, The Second Affiliated Hospital , Xi'an Jiaotong University Medical College , Xi'an, Shaanxi, China.
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D056151:Airway Remodeling / Q000235:genetics; D001249:Asthma / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D008168:Lung / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C546110:MIRN138 microRNA, human; C000631429:PDK1 protein, human
keywords: 3-phosphoinositide-dependent protein kinase-1 (PDK1); airway smooth muscle cells (ASMCs); miR-138; phosphoinositide 3–kinase/protein kinase B (PI3K/AKT) signaling pathway