title: HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma.
abstract: BACKGROUND
  Long noncoding RNA Hox transcript antisense intergenic RNA (HOTAIR) has been characterized as a negative prognostic factor in breast and colon cancer patients. The clinical significance and function of HOTAIR in glioma remains unclear.
  
  
  METHODS
  We analyzed the clinical significance of HOTAIR in 3 different glioma cohorts with gene expression data, including correlation with tumor grade, prognosis, and molecular subtype. The function of HOTAIR in glioma was explored by performing gene set enrichment analysis and in vitro and in vivo experiments.
  
  
  RESULTS
  HOTAIR expression was closely associated with glioma grade and poor prognosis. Multivariate Cox regression analysis revealed that HOTAIR was an independent prognostic factor in glioblastoma multiforme patients. HOTAIR expression correlated with glioma molecular subtype, including those of The Cancer Genome Atlas. HOTAIR was preferentially expressed in the classical and mesenchymal subtypes compared with the neural and proneural subtypes. A gene set enrichment analysis designed to show gene set differences between patients with high and low HOTAIR expression indicated that HOTAIR expression was associated with gene sets involved in cell cycle progression. HOTAIR reduction induced colony formation suppression, cell cycle G0/G1 arrest, and orthotopic tumor growth inhibition.
  
  
  CONCLUSIONS
  Our data establish that HOTAIR is an important long noncoding RNA that primarily serves as a prognostic factor for glioma patient survival, as well as a biomarker for identifying glioma molecular subtypes, a critical regulator of cell cycle progression.
authors.affiliation: Corresponding Authors: Yong-Ping You, PhD, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. yypl9@njmu.edu.cn); Tao Jiang, PhD, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, (jiangtao369@sohu.com); Chun-Sheng Kang, PhD, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China (kang97061@gmail.com.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Zhao-Shi
authors.initials: ZS
authors.lastname: Bao
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Lu-Yue
authors.initials: LY
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Shi-Zhu
authors.initials: SZ
authors.lastname: Yu
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Pu
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: You
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
keywords: HOTAIR; cell cycle; glioma; molecular subtype; survival