Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8 (HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.

中文翻译：

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Homeobox B8靶向无菌Alpha基序域蛋白9，并驱动神经胶质瘤进展。

神经胶质瘤是中枢神经系统最常见的肿瘤。多形胶质母细胞瘤（GBM）是成人中最恶性和侵略性脑癌。迫切需要进一步了解GBM攻击性本质的机制。在这里，我们确定homeobox B8（HOXB8）是homeobox家族的成员，它是GBM侵略性的关键贡献者。可公开访问的RNA序列数据集和我们的患者队列的数据挖掘证实，GBM患者肿瘤组织中HOXB8的表达较高，并且肿瘤的表达水平和病理分级之间呈强正相关，而表达水平与肿瘤之间呈负相关。总体生存率。接下来，我们证明HOXB8可以促进胶质母细胞瘤细胞的增殖和迁移，并且对于PI3K / AKT途径的激活和上皮-间质转化相关基因的表达至关重要，可能是通过直接结合SAMD9（不育阿尔法基序域） -包含蛋白质9）并激活其转录。总的来说，我们确定HOXB8是GBM侵略性的关键贡献者，它为GBM的潜在治疗靶点提供了见识，并为改善其治疗效果开辟了新途径。