Jun-Xia Zhang1, Lei Han, Zhao-Shi Bao, Ying-Yi Wang, Lu-Yue Chen, Wei Yan, Shi-Zhu Yu, Pei-Yu Pu, Ning Liu, Yong-Ping You, Tao Jiang, Chun-Sheng Kang. 1. 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.
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. CONCLUSION: 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.
BACKGROUND: Long noncoding RNA Hox transcript antisense intergenic RNA (HOTAIR) has been characterized as a negative prognostic factor in breast and colon cancerpatients. 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 multiformepatients. 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. CONCLUSION: Our data establish that HOTAIR is an important long noncoding RNA that primarily serves as a prognostic factor for gliomapatient survival, as well as a biomarker for identifying glioma molecular subtypes, a critical regulator of cell cycle progression.
Authors: Monika E Hegi; Robert-Charles Janzer; Wanyu L Lambiv; Thierry Gorlia; Mathilde C M Kouwenhoven; Christian Hartmann; Andreas von Deimling; Danielle Martinet; Nathalie Besuchet Schmutz; Annie-Claire Diserens; Marie-France Hamou; Pierre Bady; Michael Weller; Martin J van den Bent; Warren P Mason; René-Olivier Mirimanoff; Roger Stupp; Karima Mokhtari; Pieter Wesseling Journal: Acta Neuropathol Date: 2012-01-15 Impact factor: 17.088
Authors: Ana Xavier-Magalhães; Ana I Oliveira; Joana Vieira de Castro; Marta Pojo; Céline S Gonçalves; Tatiana Lourenço; Marta Viana-Pereira; Sandra Costa; Paulo Linhares; Rui Vaz; Rui Nabiço; Júlia Amorim; Afonso A Pinto; Rui M Reis; Bruno M Costa Journal: J Neurooncol Date: 2017-01-12 Impact factor: 4.130