title: miR-181d/MALT1 regulatory axis attenuates mesenchymal phenotype through NF-κB pathways in glioblastoma.
abstract: The mesenchymal (MES) subtype of glioblastoma (GBM) indicated a more malignant phenotype and worse prognosis compared with their proneural (PN) counterpart. The plasticity between PN and MES transcriptome signatures provided an approach for clinical intervention. However, few miRNAs have been identified to participate in the shift between subtypes. Here, we utilized transcriptomic data and experimental evidences to prove that miR-181d was a novel regulator of NFκB signaling pathway by directly repressing MALT1, leading to induced PN markers and reduced MES genes. Functionally, ectopic expression of miR-181d suppressed GBM cell proliferation, colony formation and anchor-independent growth, as well as migration, invasion and tube formation. Moreover, miR-181d overexpression increased radio- and chemo-sensitivity for GBM cells. Rescue of MALT1 could partially reverse the effects of miR-181d in GBM malignant behaviors. Clinically, miR-181d could serve as a prognostic indicator for GBM patients. Taken together, we concluded that loss of miR-181d contributes to aggressive biological processes associated with MES phenotype via NFκB signaling, which broaden our insights into the underlying mechanisms in subtype transition and miRNA-based tailored medicine for GBM management.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China. Electronic address: taojiang1964@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Chinese Glioma Cooperative Group (CGCG), China. Electronic address: wyz232@163.com.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction
chemical_list: C000608460:MIRN-181 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009363:Neoplasm Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
keywords: Glioma; Mesenchymal transition; NF-κB signaling; Non-coding RNA; Transcriptome subtype