Peroxiredoxin-6 regulates p38-mediated epithelial-mesenchymal transition in HCT116 colon cancer cells.

IF 1.9 3区 生物学 Q2 BIOLOGY
Unbin Chae, Bokyung Kim, HanSeop Kim, Young-Ho Park, Seung Hwan Lee, Sun-Uk Kim, Dong-Seok Lee
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引用次数: 4

Abstract

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.

Abstract Image

Abstract Image

Abstract Image

过氧化物还原素-6调节p38介导的HCT116结肠癌细胞上皮-间质转化。
背景:过氧化物还毒素(Prxs)是一种抗氧化酶,可以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-间充质转化(epithelial -mesenchymal transition, EMT)是一种诱导癌细胞失去上皮特征而获得间充质表型的转化过程。EMT通过多种途径,如丝裂原活化蛋白激酶(MAPKs)和表观遗传调节因子,促进转移和癌细胞进展。方法:利用Prx6过表达和下调的HCT116细胞,研究Prx6与结肠癌的作用机制。Western blotting检测Prx6、GAPDH、Snail、Twist1、E-cadherin、Vimentin、N-cadherin、ERK、p-ERK、p38、p-p38、JNK、p-JNK的表达。此外,我们还进行了异种移植实验的动物研究,以探索Prx6在肿瘤发生中的功能。通过IncuCyte细胞增殖和集落形成试验测定细胞增殖和迁移。结果:我们证实了Prx6和EMT信号在HCT116中的表达高于其他结肠癌细胞系。Prx6通过调控HCT116结肠癌细胞中EMT相关转录抑制因子和间充质基因调控EMT信号通路。prx6过表达条件下,HCT116细胞增殖明显增强。siprx6处理后,HCT116细胞的增殖能力下降。注射HCT116细胞11天后,Prx6在注射HCT116的小鼠中过表达,肿瘤体积较对照小鼠明显增大。此外,Prx6在结肠癌细胞中通过p38磷酸化调节EMT信号。结论:在HCT116结肠癌细胞中,Prx6通过p38磷酸化调控EMT信号通路。
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来源期刊
CiteScore
5.20
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Journal of Biological Research-Thessaloniki is a peer-reviewed, open access, international journal that publishes articles providing novel insights into the major fields of biology. Topics covered in Journal of Biological Research-Thessaloniki include, but are not limited to: molecular biology, cytology, genetics, evolutionary biology, morphology, development and differentiation, taxonomy, bioinformatics, physiology, marine biology, behaviour, ecology and conservation.
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