Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells.
Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells.
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DOI：
10.1159/000495934
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Kuo, Hsing-Chun
中科院分区：
文献类型：
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作者：
Huang, Wen-Shih;Huang, Cheng-Yi;Kuo, Hsing-Chun
背景/目的：结直肠癌（CRC）是世界范围内第三大常见癌症，也是癌症相关死亡的第二大原因。PRDXs是抗氧化酶，在细胞分化、增殖和凋亡中起重要作用，并且在恶性肿瘤发展中具有多种功能。方法：采用Boyden小室法、流式细胞术、靶向PRDX 6的慢病毒shRNA及pCMV-6-PRDX 6质粒瞬时转染等方法，研究PRDX 6在大肠癌细胞增殖和侵袭能力中的作用。结果：PRDX 6在结直肠腺瘤转移中的表达差异有统计学意义（P = 0.03），PRDX 6在结直肠腺瘤转移中的表达差异有统计学意义（P = 0.03）。在体外HCT-116中，PRDX 6沉默显著抑制CRC细胞迁移和侵袭，同时还诱导细胞周期停滞以及活性氧（ROS）的产生; PRDX 6的特异性过表达具有相反的作用。从机制上讲，PRDX 6失活通过PI 3 K/ AKT/p38/p50途径的激活显示PRDX 6、N-钙粘蛋白、β-连环蛋白、波形蛋白、Slug、Snail和Twist-1的水平降低，但它们也被PRDX 6转染子显著抑制。PRDX 6启动子的组蛋白H3赖氨酸4（H3 K4 me 3）的二甲基化也通过PI 3 K/Akt/NFkB途径的激活而增加转录激活。结论：我们的研究结果表明PRDX 6表达在结直肠癌转移中起着特征性的促生长作用。这项研究表明，PRDX 6可能作为一个生物标志物的淋巴结阳性状态，并可能有一个重要的内源性调节剂的癌细胞在CRC的致瘤性的作用。PRDX 6也可能是一个有效的治疗靶点。
BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear.METHODS: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins.RESULTS: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, beta-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways.CONCLUSION: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.