title: SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma.
abstract: Glioblastoma (GBM) is associated with disproportionately high morbidity and mortality, reflecting the need to develop new diagnostic and therapeutic targets for this disease. Recently, accumulating evidence has suggested that small nucleolar RNAs (snoRNAs) are gaining prominence and are more actively involved in tumorigenesis than previously thought. However, no report concerning the implication of snoRNAs in glioma has been published to date. In our study, SNORD76 was first found to be inversely associated with Hox Transcript Antisense Intergenic RNA (HOTAIR) knockdown, and surprisingly, forcibly expressed SNORD76 inhibited proliferation and growth of glioma cells. Moreover, downregulation of SNORD76 led to a more malignant phenotype. The pleiotropy of SNORD76 overexpression could be achieved at least partially through inducing cell cycle arrest at S phase by affecting the Rb-associated cell cycle regulation. Enforced SNORD76 expression in orthotopic tumors resulted in decreased tumor growth and the reduction of tumor volume. Additionally, in surgically resected glioma tissues, SNORD76, not its host gene, was associated with the WHO classification and was selectively downregulated in GBM (WHO grade IV). Collectively, our study adds to a growing body of evidence for the participation of snoRNAs in gliomagenesis and is the first to implicate a snoRNA in glioblastoma.
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Luyue
authors.initials: L
authors.lastname: Chen
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wei
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Shi
authors.affiliation: 1] Chinese Glioma Cooperative Group (CGCG), China [2] Beijing Tian Tan Hospital, Capital Medical University.
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.affiliation: 1] Chinese Glioma Cooperative Group (CGCG), China [2] Beijing Sanbo Brain Hospital, Capital Medical University.
authors.forename: Shouwei
authors.initials: S
authors.lastname: Li
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1] Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital [2] Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government [3] Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics*; D059807:S Phase Cell Cycle Checkpoints; D047368:Tumor Burden
chemical_list: C561567:GAS5 long non-coding RNA, human; D062085:RNA, Long Noncoding