BACKGROUND Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. METHODS The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. RESULTS We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. CONCLUSION This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.

中文翻译：

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赖氨酸脱甲基酶2（KDM2B）通过MOB1调节河马途径，以促进胰腺导管腺癌（PDAC）的进展。

背景技术Mps1结合蛋白（MOB1）是哺乳动物Hippo途径的核心成分之一，在癌症的发展中起着重要的作用。然而，其在胰腺导管腺癌（PDAC）中的表达，功能和调控尚未被揭示。方法测定MOB1和赖氨酸脱甲基酶2B（KDM2B）在PDAC及邻近正常胰腺组织中的表达。此外，还研究了MOB1表达改变的潜在机制及其对PDAC生物学的影响。结果我们首次揭示了MOB1在PDAC中的表达降低，并且是存活率低的统计学显着的独立预测因子，恢复的MOB1表达抑制了PDAC细胞的增殖，迁移和侵袭。进一步的研究表明，KDM2B直接与MOB1的启动子区域结合，并抑制了MOB1的启动子活性，并在转录上抑制了MOB1的表达。此外，KDM2B调节Hippo通路，并通过MOB1促进PDAC增殖，迁移和入侵。结论这项研究证明了新型的KDM2B / MOB1 / Hippo信号传导在PDAC进展中的机制和作用。