title: A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma.
abstract: The comprehensive lncRNA expression signature in glioma has not yet been fully elucidated. We performed a high-throughput microarray to detect the ncRNA expression profiles of 220 human glioma tissues. Here, we found that a novel lncRNA, HOXA11-AS, was the antisense transcript of the HOX11 gene. It was shown that HOXA11-AS was closely associated with glioma grade and poor prognosis. Multivariate Cox regression analysis revealed that HOXA11-AS was an independent prognostic factor in glioblastoma multiforme patients, and its expression was correlated with the glioma molecular subtypes of the Cancer Genome Atlas. Gene set enrichment analysis indicated that the gene sets most correlated with HOXA11-AS expression were involved in cell cycle progression. Over-expression of the HOXA11-AS transcript promoted cell proliferation in vitro, while knockdown of HOXA11-AS expression repressed cell proliferation via regulation of cell cycle progression. The growth-promoting and growth-inhibiting effects of HOXA11-AS were also demonstrated in a xenograft mouse model. Our data confirms, for the first time, that HOXA11-AS is an important long non-coding RNA that primarily serves as a prognostic factor for glioma patient survival. HOXA11-AS could serve as a biomarker for identifying glioma molecular subtypes and as therapeutic target for glioma patients.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China.
authors.forename: Qixue
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Glioma Center, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Glioma Center, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China.
authors.forename: Junhu
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Glioma Center, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China. Electronic address: superhanlei@hotmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000032:analysis* / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C484298:HOXA11 protein, human; D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding
keywords: Cell cycle; Glioma; HOXA cluster; HOXA11-AS; Long noncoding RNAs