title: Primate-specific miR-663 functions as a tumor suppressor by targeting PIK3CD and predicts the prognosis of human glioblastoma.
abstract: OBJECTIVE
  To determine the prognostic significance of miR-663 in glioblastoma, its effect in tumor progression, and the underlying mechanism.
  
  
  METHODS
  Specimens from 256 cases of patients with glioma, including 239 patients with follow-up information, were used to analyze the association between miR-663 and patients' prognosis by Kaplan-Meier and multivariate Cox regression analyses. The effects of miR-663 on glioblastoma cell proliferation and invasion were examined both in vitro and in vivo. Bioinformatics prediction and signal network analysis were applied to identify the putative targets of miR-663, which were further verified by luciferase reporter assay, rescue experiments as well as the immunohistochemistry (IHC) and Western blotting examination of downstream effectors. Quantitative reverse transcriptase PCR (qRT-PCR) and IHC were applied to investigate the clinical association between miR-663 and its target in human glioblastoma specimens.
  
  
  RESULTS
  miR-663 was inversely correlated with glioma grades but positively correlated with patients' survival. Furthermore, two distinct subgroups of patients with glioblastoma with different prognoses were identified on the basis of miR-663 expression in our specimens and that from The Cancer Genome Atlas (TCGA) database. Overexpression of miR-663 significantly suppressed the proliferation and invasion of glioblastoma cells in vitro and in vivo. Mechanistically, we discovered PIK3CD as a direct target of miR-663 and found that phosphorylated AKT and three key downstream effectors of PIK3CD, i.e., CCND1, MMP2, and MMP7, were downregulated by miR-663 overexpression. Moreover, PIK3CD was inversely correlated with miR-663 in glioblastoma specimens and predicted poor prognosis of patients with glioblastoma.
  
  
  CONCLUSIONS
  miR-663 is a novel prognostic biomarker and a potential therapeutic candidate for glioblastoma.
authors: Authors' Affiliations: Institute of Pathology and Southwest Cancer Center, Southwest Hospital; Key Laboratory of Tumor Immunopathology of Ministry of Education of China; Department of Health Statistics, College of Preventive Medicine, Third Military Medical University, Chongqing; Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin; and Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Yu
authors: Y
authors: Shi
authors: Cong
authors: C
authors: Chen
authors: Xia
authors: X
authors: Zhang
authors: Qing
authors: Q
authors: Liu
authors: Jin-Ling
authors: JL
authors: Xu
authors: Hua-Rong
authors: HR
authors: Zhang
authors: Xiao-Hong
authors: XH
authors: Yao
authors: Tao
authors: T
authors: Jiang
authors: Zhi-Cheng
authors: ZC
authors: He
authors: Yong
authors: Y
authors: Ren
authors: Wei
authors: W
authors: Cui
authors: Chuan
authors: C
authors: Xu
authors: Ling
authors: L
authors: Liu
authors: You-Hong
authors: YH
authors: Cui
authors: Shi-Zhu
authors: SZ
authors: Yu
authors: Yi-Fang
authors: YF
authors: Ping
authors: Xiu-Wu
authors: XW
authors: Bian
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D023041:Xenograft Model Antitumor Assays
chemical_list: C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D058534:Class I Phosphatidylinositol 3-Kinases; C486018:PIK3CD protein, human