The lysyl oxidase (LOX) family is closely related to the progression of glioma. To ensure the clinical significance of LOX family in glioma, The Cancer Genome Atlas (TCGA) database was mined and the analysis indicated that higher LOXL1 expression was correlated with more malignant glioma progression. The functions of LOXL1 in promoting glioma cell survival and inhibiting apoptosis were studied by gain- and loss-of-function experiments in cells and animals. LOXL1 was found to exhibit antiapoptotic activity by interacting with multiple antiapoptosis modulators, especially BAG family molecular chaperone regulator 2 (BAG2). LOXL1-D515 interacted with BAG2-K186 through a hydrogen bond, and its lysyl oxidase activity prevented BAG2 degradation by competing with K186 ubiquitylation. Then, we discovered that LOXL1 expression was specifically upregulated through the VEGFR-Src-CEBPA axis. Clinically, the patients with higher LOXL1 levels in their blood had much more abundant BAG2 protein levels in glioma tissues. Conclusively, LOXL1 functions as an important mediator that increases the antiapoptotic capacity of tumor cells, and approaches targeting LOXL1 represent a potential strategy for treating glioma. In addition, blood LOXL1 levels can be used as a biomarker to monitor glioma progression.

中文翻译：

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LOXL1 通过稳定 BAG2 赋予抗细胞凋亡并促进胶质瘤生成。

赖氨酰氧化酶 (LOX) 家族与胶质瘤的进展密切相关。为了确保 LOX 家族在胶质瘤中的临床意义，挖掘了癌症基因组图谱 (TCGA) 数据库，分析表明较高的 LOXL1 表达与更恶性的胶质瘤进展相关。LOXL1在促进胶质瘤细胞存活和抑制细胞凋亡中的作用通过细胞和动物的功能获得和丧失实验进行研究。发现 LOXL1 通过与多种抗细胞凋亡调节剂，尤其是 BAG 家族分子伴侣调节剂 2 (BAG2) 相互作用而表现出抗细胞凋亡活性。LOXL1-D515 通过氢键与 BAG2-K186 相互作用，其赖氨酰氧化酶活性通过与 K186 泛素化竞争来阻止 BAG2 降解。然后，我们发现 LOXL1 表达通过 VEGFR-Src-CEBPA 轴特异性上调。临床上，血液中 LOXL1 水平较高的患者在神经胶质瘤组织中具有更丰富的 BAG2 蛋白水平。总之，LOXL1 作为一种重要的介质，可以增加肿瘤细胞的抗凋亡能力，而针对 LOXL1 的方法代表了治疗神经胶质瘤的潜在策略。此外，血液 LOXL1 水平可用作监测神经胶质瘤进展的生物标志物。和靶向 LOXL1 的方法代表了治疗神经胶质瘤的潜在策略。此外，血液 LOXL1 水平可用作监测神经胶质瘤进展的生物标志物。和靶向 LOXL1 的方法代表了治疗神经胶质瘤的潜在策略。此外，血液 LOXL1 水平可用作监测神经胶质瘤进展的生物标志物。