Introduction: RBM5 acts as a tumor suppressor gene in lung and breast cancers; however, its role in the pathogenesis of medulloblastoma (MB) remains unclear. We previously identified 4 RBM5 mutations in whole exome sequencing analysis of 40 MB patients. This study examined the role of RBM5 in MB progression. Methods: The expression patterns of RBM5 in tissues of 40 MB patients were analyzed using immunohistochemistry. Associations between RBM5 expression and overall survival (OS) were evaluated using Kaplan-Meier analysis. The RBM5 role in Daoy cells’ proliferation, migration, and Wnt/β-catenin signaling was analyzed after RBM5 knockdown and overexpression. Results: The expression level of RBM5 mRNA and protein was significantly lower in MB than that in adjacent normal control tissues, and low RBM5 expression was significantly associated with reduced OS (p = 0.034). RBM5 knockdown induced Daoy and ONS-76 cells proliferation, while RBM5 overexpression repressed cell proliferation and migration in vitro (all p < 0.05). β-Catenin, LEF1, and cyclin D1 mRNA levels were upregulated, while DKK1 expression was downregulated in Daoy cells following RBM5 knockdown. Conclusion: RBM5 may function as a tumor suppressor in MB by regulating Wnt/β-catenin signaling, and its reduced expression is associated with lower OS.

中文翻译：

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RBM5 通过调节 Wnt/β-Catenin 信号传导在髓母细胞瘤中充当肿瘤抑制因子

简介：RBM5在肺癌和乳腺癌中作为抑癌基因；然而，其在髓母细胞瘤 (MB) 发病机制中的作用仍不清楚。我们之前在 40 MB 患者的全外显子组测序分析中发现了 4 个 RBM5 突变。该研究检查了 RBM5 在 MB 进展中的作用。方法：使用免疫组织化学分析 40 MB 患者组织中 RBM5 的表达模式。使用 Kaplan-Meier 分析评估 RBM5 表达与总生存期 (OS) 之间的关联。在 RBM5 敲低和过表达后，分析了 RBM5 在 Daoy 细胞增殖、迁移和 Wnt/β-catenin 信号传导中的作用。结果：MB中RBM5 mRNA和蛋白的表达水平显着低于邻近正常对照组织，低 RBM5 表达与降低的 OS 显着相关（p = 0.034）。RBM5 敲低诱导 Daoy 和 ONS-76 细胞增殖，而 RBM5 过表达抑制体外细胞增殖和迁移（所有 p < 0.05）。β-Catenin、LEF1 和细胞周期蛋白 D1 mRNA 水平上调，而 RBM5 敲低后 Daoy 细胞中 DKK1 的表达下调。结论：RBM5 可能通过调节 Wnt/β-catenin 信号在 MB 中发挥肿瘤抑制作用，其表达降低与较低的 OS 相关。