HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways.
HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways.
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HOXA13 是一种潜在的 GBM 诊断标志物，通过激活 Wnt 和 TGF-β 途径促进神经胶质瘤侵袭
DOI：
10.18632/oncotarget.4813
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Wang L
中科院分区：
文献类型：
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作者：
Duan R;Han L;Wang Q;Wei J;Chen L;Zhang J;Kang C;Wang L
同源异型盒（HOX）基因，包括HOXA 13，与人类癌症有关。我们发现HOXA 13的表达与胶质瘤的分级和预后有关。生物信息学分析显示，HOXA 13相关基因大多富集于肿瘤相关信号通路中，主要参与转录调控。我们用Lenti-si HOXA 13转染了四种胶质瘤细胞系。HOXA 13可促进细胞增殖和侵袭，抑制细胞凋亡。HOXA 13减少细胞核中的β-连环蛋白、磷酸化SMAD 2和磷酸化SMAD 3，并增加细胞质中的磷酸化β-连环蛋白。此外，原位肿瘤中HOXA 13的下调降低了肿瘤生长。我们认为HOXA 13部分通过Wnt和TGF-β诱导的EMT促进胶质瘤进展，并且是胶质母细胞瘤的潜在诊断生物标志物和高级别胶质瘤的独立预后因素。
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.