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Methyl-CpG-binding domain 3 inhibits stemness of pancreatic cancer cells via Hippo signaling.
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-05-15 , DOI: 10.1016/j.yexcr.2020.112091 Huizhi Wang 1 , Wen Feng 2 , Wei Chen 1 , Junbo He 1 , Jingyu Min 1 , Yawen Liu 1 , Feifan Li 1 , Jiaxi Chen 1 , Shuhui Wu 1 , Baoding Chen 1 , Aihua Gong 3 , Min Xu 1
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-05-15 , DOI: 10.1016/j.yexcr.2020.112091 Huizhi Wang 1 , Wen Feng 2 , Wei Chen 1 , Junbo He 1 , Jingyu Min 1 , Yawen Liu 1 , Feifan Li 1 , Jiaxi Chen 1 , Shuhui Wu 1 , Baoding Chen 1 , Aihua Gong 3 , Min Xu 1
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Methyl-CpG-binding domain 3 (MBD3), as an induced stem cells reprogramming barrier, has an abnormal expression in various prevalent malignancies. However, in pancreatic cancer cell stemness, the roles of MBD3 remain unclear. In our study, the effects of MBD3 were investigated on the proliferation, stemness and the underlying mechanism in pancreatic cancer cells. Firstly, MBD3 knockdown was proved to promote proliferation and sphere formation of pancreatic cancer cells and tumorigenesis, while MBD3 upregulation inhibited the above results. Also, MBD3 downregulation notably increased stemness markers level of OCT4, NANOG and SOX2, and MBD3 upregulation resulted in the opposite effects. Mechanically, it was found that MBD3 involved in activation of Hippo pathway. There was a negative correlation between MBD3 and YAP expression in TCGA database. MBD3 knockdown improved YAP expression, and promoted YAP nuclear translocation increased TEAD luciferase activity, while MBD3 overexpression reversed the above results. Further evidence revealed that YAP could bind to MBD3, and decreased MBD3 expression. Collectively, MBD3 bound to YAP to significantly inhibit proliferation and weaken stemness maintenance in pancreatic cancer cells, as well as reduce tumorigenesis via Hippo signaling. Thus, MBD3 may serve as a potential molecular biomarker for exploring new therapeutic strategies to treat pancreatic cancer.
中文翻译：
甲基 CpG 结合结构域 3 通过 Hippo 信号传导抑制胰腺癌细胞的干细胞性。
甲基 CpG 结合域 3 (MBD3) 作为诱导干细胞重编程屏障，在多种常见恶性肿瘤中表达异常。然而，在胰腺癌细胞干细胞中，MBD3 的作用仍不清楚。在我们的研究中，研究了 MBD3 对胰腺癌细胞增殖、干性及其潜在机制的影响。首先，MBD3敲低被证明可以促进胰腺癌细胞的增殖和球体形成以及肿瘤发生，而MBD3上调则抑制上述结果。此外，MBD3 下调显着增加了 OCT4、NANOG 和 SOX2 的干性标记物水平，而 MBD3 上调则导致相反的效果。从机械角度来看，MBD3 参与了 Hippo 通路的激活。 TCGA数据库中MBD3与YAP表达呈负相关。 MBD3敲低改善了YAP表达，并促进YAP核转位增加了TEAD荧光素酶活性，而MBD3过表达则逆转了上述结果。进一步的证据表明，YAP 可以与 MBD3 结合，并降低 MBD3 的表达。总的来说，MBD3 与 YAP 结合可显着抑制胰腺癌细胞的增殖并削弱其干性维持，并通过 Hippo 信号传导减少肿瘤发生。因此，MBD3可能作为探索胰腺癌新治疗策略的潜在分子生物标志物。
更新日期：2020-05-16
中文翻译：
甲基 CpG 结合结构域 3 通过 Hippo 信号传导抑制胰腺癌细胞的干细胞性。
甲基 CpG 结合域 3 (MBD3) 作为诱导干细胞重编程屏障，在多种常见恶性肿瘤中表达异常。然而，在胰腺癌细胞干细胞中，MBD3 的作用仍不清楚。在我们的研究中，研究了 MBD3 对胰腺癌细胞增殖、干性及其潜在机制的影响。首先，MBD3敲低被证明可以促进胰腺癌细胞的增殖和球体形成以及肿瘤发生，而MBD3上调则抑制上述结果。此外，MBD3 下调显着增加了 OCT4、NANOG 和 SOX2 的干性标记物水平，而 MBD3 上调则导致相反的效果。从机械角度来看，MBD3 参与了 Hippo 通路的激活。 TCGA数据库中MBD3与YAP表达呈负相关。 MBD3敲低改善了YAP表达，并促进YAP核转位增加了TEAD荧光素酶活性，而MBD3过表达则逆转了上述结果。进一步的证据表明，YAP 可以与 MBD3 结合，并降低 MBD3 的表达。总的来说，MBD3 与 YAP 结合可显着抑制胰腺癌细胞的增殖并削弱其干性维持，并通过 Hippo 信号传导减少肿瘤发生。因此，MBD3可能作为探索胰腺癌新治疗策略的潜在分子生物标志物。
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