过氧化物氧化还原酶6调节HCT116结肠癌细胞中p38介导的上皮-间质转化。
Peroxiredoxin-6 regulates p38-mediated epithelial-mesenchymal transition in HCT116 colon cancer cells.
作者信息
Chae Unbin, Kim Bokyung, Kim HanSeop, Park Young-Ho, Lee Seung Hwan, Kim Sun-Uk, Lee Dong-Seok
机构信息
Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea.
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea.
出版信息
J Biol Res (Thessalon). 2021 Nov 23;28(1):22. doi: 10.1186/s40709-021-00153-6.
BACKGROUND
Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial-mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators.
METHODS
We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays.
RESULTS
We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells.
CONCLUSION
We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.
背景
过氧化物酶（Prxs）是一种抗氧化酶，可保护细胞免受多种因素诱导的氧化应激。它们调节多种信号通路，如代谢、免疫反应和细胞内活性氧（ROS）稳态。上皮-间质转化（EMT）是一个转变过程，可导致癌细胞上皮特征丧失和间质表型获得。EMT通过多种途径促进转移和癌细胞进展，如丝裂原活化蛋白激酶（MAPKs）和表观遗传调节因子。
方法
我们使用Prx6过表达和下调的HCT116细胞来研究Prx6与结肠癌之间的机制。通过蛋白质免疫印迹法检测Prx6、甘油醛-3-磷酸脱氢酶（GAPDH）、Snail、Twist1、E-钙黏蛋白、波形蛋白、N-钙黏蛋白、细胞外信号调节激酶（ERK）、磷酸化ERK（p-ERK）、p38、磷酸化p38（p-p38）、应激活化蛋白激酶（JNK）和磷酸化JNK（p-JNK）的表达。此外，进行了动物异种移植实验研究，以探讨Prx6在肿瘤发生中的作用。通过IncuCyte细胞增殖和集落形成实验测定细胞增殖和迁移。
结果
我们证实，与其他结肠癌细胞系相比，Prx6和EMT信号在HCT116中高度表达。Prx6通过调节HCT116结肠癌细胞中与EMT相关的转录抑制因子和间质基因来调控EMT信号通路。在Prx6过表达条件下，HCT116细胞增殖显著增加。此外，在经小干扰RNA（siPrx6）处理的细胞中，HCT116细胞增殖减少。注射HCT116细胞后第11天，Prx6在注射HCT116的小鼠中过表达，与对照小鼠相比，肿瘤体积显著增加。此外，Prx6通过结肠癌细胞中的p38磷酸化调节EMT信号。
结论
我们认为Prx6通过调节HCT116结肠癌细胞中的p38磷酸化来调控EMT信号通路。
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