title: miR-146b-5p functions as a tumor suppressor by targeting TRAF6 and predicts the prognosis of human gliomas.
abstract: Down-regulation of miR-146b-5p contributes to tumorigenesis in several human cancers. However, the relevance of miR-146b-5p to prognosis, proliferation and apoptosis in gliomas remains unknown. In the present study, we demonstrated that miR-146b-5p expression was inversely correlated with grades and Ki-67 index in 147 human glioma specimens, but positively correlated with patients' survival. Furthermore, two distinct subgroups of patients with grade I-IV gliomas with different prognoses were identified according to miR-146b-5p expression in our specimens. Cox regression showed that miR-146b-5p was an independent predictor for patients' survival. Overexpression of miR-146b-5p dramatically suppressed glioma cell proliferation and induced apoptosis. Mechanistically, we validated TRAF6 as a direct functional target of miR-146b-5p and found that miR-146b-5p overexpression significantly decreased phosphorylated TAK1 and IκBα, the pivotal downstream effectors of TRAF6. Moreover, TRAF6 expression was positively correlated with glioma grades and Ki-67 index but inversely correlated with miR-146b-5p expression and predicted poor prognosis of glioma patients. In glioblastoma cell lines, silencing of TRAF6 could mimic the anti-tumor effect of miR-146b-5p. Our findings identify miR-146b-5p as a tumor suppressor and novel prognostic biomarker of gliomas, and suggest miR-146b-5p and TRAF6 as potential therapeutic candidates for malignant gliomas.
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Jing
authors: J
authors: Liu
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Jinling
authors: J
authors: Xu
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Huining
authors: H
authors: Li
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Cuiyun
authors: C
authors: Sun
authors: Department of Biochemistry, Basic Medical College of Tianjin Medical University, Tianjin 300070, China.
authors: Lin
authors: L
authors: Yu
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Yanyan
authors: Y
authors: Li
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Cuijuan
authors: C
authors: Shi
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Xuexia
authors: X
authors: Zhou
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Xiuwu
authors: X
authors: Bian
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Yifang
authors: Y
authors: Ping
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Yanjun
authors: Y
authors: Wen
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Laboratory of Hormone and Development, Ministry of Health, Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Shujun
authors: S
authors: Zhao
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Hui
authors: H
authors: Xu
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Linlin
authors: L
authors: Ren
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Tongling
authors: T
authors: An
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Qian
authors: Q
authors: Wang
authors: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China.|Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors: Shizhu
authors: S
authors: Yu
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060787:Neoplasm Grading; D034622:RNA Interference; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6
keywords: TRAF6; apoptosis; gliomas; miR-146b-5p; prognosis; proliferation