Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression
Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression
复制标题
赖氨酸脱甲基酶 2 (KDM2B) 通过 MOB1 调节 hippo 通路促进胰腺导管腺癌 (PDAC) 进展
DOI：
10.1186/s13046-019-1489-0
复制
发表时间：
2020-01-15
影响因子：
11.3
通讯作者：
Cui, Jiujie
中科院分区：
文献类型：
--
作者：
Quan, Ming;Chen, Zhiqin;Cui, Jiujie
背景Mps1结合蛋白（MOB1）是哺乳动物Hippo通路的核心成分之一，在癌症发展中发挥重要作用。但其在胰腺导管腺癌(PDAC)中的表达、功能及调控尚未被揭示。方法检测PDAC及癌旁正常胰腺组织中MOB1和赖氨酸脱甲基酶2B(KDM2B)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，MOB1 在 PDAC 中表达降低，是生存不良的统计学显着的独立预测因子，而 MOB1 表达的恢复抑制了 PDAC 细胞的增殖、迁移和侵袭。进一步的研究表明，KDM2B直接结合MOB1的启动子区域，抑制MOB1的启动子活性，从而转录抑制MOB1的表达。此外，KDM2B通过MOB1调节Hippo通路并促进PDAC增殖、迁移和侵袭。结论本研究证明了新型KDM2B/MOB1/Hippo信号在PDAC进展中的机制和作用。
BackgroundMps1 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.MethodsThe 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.ResultsWe 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.ConclusionThis study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.