title: An axis involving SNAI1, microRNA-128 and SP1 modulates glioma progression.
abstract: BACKGROUND
  Glioblastoma is an extraordinarily aggressive disease that requires more effective therapeutic options. Snail family zinc finger 1, dysregulated in many neoplasms, has been reported to be involved in gliomas. However, the biological mechanisms underlying SNAI1 function in gliomas need further investigation.
  
  
  METHODS
  Quantitative real-time PCR was used to measure microRNA-128 (miR-128) expression level and western blot was performed to detect protein expression in U87 and U251 cells and human brain tissues. Cell cycle, CCK-8, transwell and wound-healing assays were performed. Dual-luciferase reporter assay was used for identifying the mechanism of SNAI1 and miR-128b regulation. The mechanism of miR-128 targeting SP1 was also tested by luciferase reporter assay. Immunohistochemistry and in situ hybridisation staining were used for quantifying SNAI1, SP1 and miR-128 expression levels in human glioma samples.
  
  
  RESULTS
  The Chinese Glioma Genome Atlas (CGGA) data revealed that SNAI1 was up-regulated in glioma and we confirmed the findings in normal and glioma tissues. SNAI1 depletion by shRNA retarded the cell cycle and suppressed proliferation and invasion in glioma cell lines. The CGGA data showed that the Pearson correlation index between SNAI1 and miR-128 was negatively correlated. SNAI1 suppressed miR-128b expression by binding to the miR-128b specific promoter motif, and miR-128 targeted SP1 via binding to the 3'-untranslated region of SP1. Moreover, introduction of miR-128 anti-sense oligonucleotide alleviated the cell cycle retardation, proliferation and invasion inhibition induced by SNAI1 shRNA. Immunohistochemistry and in situ hybridisation analysis of SNAI1, SP1 and miR-128 unraveled their expression levels and correlations in glioma samples.
  
  
  CONCLUSIONS
  We propose that the SNAI1/miR-128/SP1 axis, which plays a vital role in glioma progression, may come to be a clinically relevant therapeutic target.
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Qingsheng
authors: Q
authors: Dong
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Ning
authors: N
authors: Cai
authors: Department of Urology, Affiliated Zhongda Hospital, Southeast University, Nanjing, China.
authors: Tao
authors: T
authors: Tao
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Rui
authors: R
authors: Zhang
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Wei
authors: W
authors: Yan
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Rui
authors: R
authors: Li
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Junxia
authors: J
authors: Zhang
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Hui
authors: H
authors: Luo
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Yan
authors: Y
authors: Shi
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Wenkang
authors: W
authors: Luan
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Yaxuan
authors: Y
authors: Zhang
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Yongping
authors: Y
authors: You
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Yingyi
authors: Y
authors: Wang
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Ning
authors: N
authors: Liu
mesh_terms: D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C545189:MIRN128 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D014157:Transcription Factors