SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway
SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway
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DOI：
10.2147/ott.s186806
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Li, Yuntao
中科院分区：
文献类型：
--
作者：
Ren, Hailiang;Wang, Zheng;Li, Yuntao
背景资料：SET和MYND结构域蛋白2（SMYD 2-OE）通过甲基化组蛋白和非组蛋白蛋白在癌症发展中起重要作用。然而，关于SMYD 2-OE在结肠癌中的相关性知之甚少。此外，奥沙利铂（L-OHP）被用作结肠癌化疗的一线药物，但耐药性限制了其疗效。出乎意料的是，结肠癌中L-OHP耐药的机制仍不清楚。本研究旨在探讨SMYD 2-OE在结肠癌组织中的表达与L-OHP耐药的关系，并进一步探讨SMYD 2-OE、L-OHP耐药与结肠癌发生的关系。结果：SMYD 2-OE在结肠癌组织中的表达高于癌旁组织，与L-OHP化疗后结肠癌患者的预后相关。在体外和体内，SMYD 2-OE的敲低增加结肠癌对L-OHP的敏感性。然而，SMYD 2-OE过表达促进体外结肠癌细胞对L-OHP的耐药性。结论：SMYD 2-OE通过MEK/ERK/AP-1信号通路调节MDR 1/P-gp表达，促进结肠癌细胞对L-OHP的耐药，为SMYD 2-OE基因敲减化疗增敏结肠癌提供了一种可能的策略。
Background: SET and MYND domain-containing protein 2 (SMYD2-OE) plays an important role in cancer development through methylating histone and non-histone proteins. However, little is known about the relevance of SMYD2-OE in colon cancer. Moreover, oxaliplatin (L-OHP) is applied as first line for colon cancer chemotherapy, but drug resistance restricts its efficacy. Unexpectedly, the mechanism of L-OHP resistance in colon cancer remains unclear. In this study, we investigated the relationship of SMYD2-OE expression and L-OHP resistance in colon cancer and further explored the underlying mechanism linking SMYD2-OE, L-OHP resistance, and colon cancer.Materials and methods: Expression levels of SMYD2-OE in colon cancer tissues of patients were tested. In vitro and in vivo assays were conducted to explore the function and mechanism of SMYD2-OE in colon cancer sensitivity to L-OHP.Results: SMYD2-OE was overexpressed in colon cancer tissues compared with non-neoplastic tissues and associated with poor prognosis of patients with colon cancer after L-OHP-based chemotherapy. Knockdown of SMYD2-OE increased colon cancer sensitivity to L-OHP in vitro and in vivo. However, SMYD2-OE overexpression promoted L-OHP resistance in colon cancer cell in vitro. In addition, SMYD2-OE could upregulate MDR1/P-glycoprotein expression depending on MEK/ERK/AP-1 signaling pathway activity.Conclusion: These results imply that SMYD2-OE promotes L-OHP resistance in colon cancer by regulating MDR1/P-glycoprotein through MEK/ERK/AP-1 signaling pathway, providing a potential strategy to sensitize che-motherapy by SMYD2-OE knockdown in colon cancer treatment.