HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways
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Ran Duan1,5, Lei Han2,3,4,5, Qixue Wang2,3,4,5, Jianwei Wei2,3,4,5, Luyue Chen2,3,4,5, Jianning Zhang3,4,5, Chunsheng Kang2,3,4,5, Lei Wang1,5,6
1Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
2Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China
3Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
4Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China
5Chinese Glioma Cooperative Group (CGCG), Beijing, China
6China National Clinical Research Center for Neurological Diseases, Beijing, China
Lei Wang, e-mail: firstname.lastname@example.org
Chunsheng Kang, e-mail: email@example.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
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.
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