title: HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways.
abstract: Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased β-catenin, phospho-smad2, and phospho-smad3 in the nucleus and increased phospho-β-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-β-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma.
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.|Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.|Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Qixue
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.|Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wei
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.|Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Luyue
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.|Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China.|Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.|Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019295:Computational Biology; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D018398:Homeodomain Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; C099959:homeobox protein HOXA13
keywords: HOXA13; Homeobox (HOX) gene; SMAD; epithelial-to-mesenchymal transition (EMT); glioma