HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways

// Ran Duan 1, 5 , Lei Han 2, 3, 4, 5 , Qixue Wang 2, 3, 4, 5 , Jianwei Wei 2, 3, 4, 5 , Luyue Chen 2, 3, 4, 5 , Jianning Zhang 3, 4, 5 , Chunsheng Kang 2, 3, 4, 5 , Lei Wang 1, 5, 6 1 Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China 2 Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China 3 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China 4 Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China 5 Chinese Glioma Cooperative Group (CGCG), Beijing, China 6 China National Clinical Research Center for Neurological Diseases, Beijing, China Correspondence to: Lei Wang, e-mail: wangleitiantan@163.com Chunsheng Kang, e-mail: kang97061@gmail.com Keywords: Homeobox (HOX) gene, HOXA13, glioma, SMAD, epithelial-to-mesenchymal transition (EMT) Received: March 21, 2015 Accepted: July 20, 2015 Published: July 31, 2015 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.