title: Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma.
abstract: BACKGROUND
  MIR155 host gene (MIR155HG) is a long noncoding RNA that has been considered as the primary micro (mi)RNA of miR-155. MIR155HG plays an essential role in hematopoiesis, inflammation, and tumorigenesis. Our study investigated the clinical significance, biological function, mechanisms, and small-molecule inhibitors of the MIR155HG/miR-155 axis in glioma.
  
  
  METHODS
  We analyzed the expression of the MIR155HG/miR-155 axis and the correlation with glioma grade and patient survival using 2 different glioma gene expression datasets. Biological significance was elucidated through a series of in vitro and in vivo experiments. Furthermore, we conducted a high-throughput screening for small molecules to identify a potential inhibitor of the MIR155HG/miR-155 axis.
  
  
  RESULTS
  Increased MIR155HG was associated with glioma grade, mesenchymal transition, and poor prognosis. Functionally, MIR155HG reduction by small interfering RNA inhibited cell proliferation, migration, invasion, and orthotopic glioma growth by repressing the generation of its derivatives miR-155-5p and miR-155-3p. Bioinformatics and luciferase reporter assays revealed that protocadherin 9 and protocadherin 7, which act as tumor suppressors by inhibiting the Wnt/β-catenin pathway, were direct targets of miR-155-5p and miR-155-3p, respectively. Finally, we identified NSC141562 as a potent small-molecule inhibitor of the MIR155HG/miR-155 axis.
  
  
  CONCLUSIONS
  Our results demonstrate that the MIR155HG/miR-155 axis plays a critical role in facilitating glioma progression and serves as a prognostic factor for patient survival in glioblastoma. High-throughput screening indicated that the MIR155HG/miR-155 axis inhibitor NSC141562 may be a useful candidate anti-glioma drug.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Er
authors.initials: E
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Weining
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Tongle
authors.initials: T
authors.lastname: Zhi
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Xiefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016016:Proportional Hazards Models
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: MIR155HG; glioma; mesenchymal transition; small-molecule inhibitor; survival