title: MiR-125b inhibits cell biological progression of Ewing's sarcoma by suppressing the PI3K/Akt signalling pathway.
abstract: OBJECTIVE
  Increasing evidence has suggested the close relationship between microRNAs (miRNAs) dysregulation and the carcinogenesis of Ewing's sarcoma (ES), among of which miR-125b has been reported to be decreased in ES tissues recently. Strikingly, ectopic expression of miR-125b could suppress cell proliferation of ES cell line A673, suggesting the tumor suppressor role of miR-125b in ES. However, the other accurate mechanistic functions and relative molecule mechanisms are largely unknown.
  
  
  METHODS
  Herein, we completed a series of experiments to investigate the role of miR-125b in Ewing's sarcoma. We restored the expression of miR-125b in ES cell line A673 through transfection with miR-125b mimics. To further understand the role of miR-125b in ES, we detected the effects of miR-125b on the cell proliferation, migration and invasion, cell cycle as well as cell apoptosis.
  
  
  RESULTS
  We found that restored expression of miR-125b in ES cell line A673 inhibited cell proliferation, migration and invasion, arrested cell cycle progression, and induced cell apoptosis. Moreover, bioinformatic prediction suggested the oncogene, phosphoinositide-3-kinase catalytic subunit delta (PIK3CD), was a target gene of miR-125b in ES cells. Further quantitative RT-PCR and western blot assays identified over-expression of miR-125b suppressed the expression of PIK3CD mRNA and protein. PIK3CD participates in regulating the PI3K signaling pathway, which has been reported to play an important role in the development of ES. Suppression of PIK3CD down-regulated the expression of phospho-AKT and phospho-mTOR proteins and inhibited the biologic progression of A673 cells.
  
  
  CONCLUSIONS
  Collectively, these data suggest that miR-125b functions as a tumor suppressor by targeting the PI3K/Akt/mTOR signaling pathway, and may provide potential therapy strategy for ES patients by targeting miRNA expression.
authors: Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.
authors: J
authors: J
authors: Li
authors: T
authors: T
authors: You
authors: J
authors: J
authors: Jing
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012334:RNA, Neoplasm; D058570:TOR Serine-Threonine Kinases; C531888:MIRN125 microRNA, human; C546842:MTOR protein, human; C486018:PIK3CD protein, human