Ovol2 induces mesenchymal-epithelial transition via targeting ZEB1 in osteosarcoma.
Ovol2 induces mesenchymal-epithelial transition via targeting ZEB1 in osteosarcoma.
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DOI：
10.2147/ott.s157119
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发表时间：
2018
影响因子：
4
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Liu J;Wu Q;Wang Y;Wei Y;Wu H;Duan L;Zhang Q;Wu Y
骨肉瘤（OS）是最常见的原发性实体骨肿瘤。卵样锌指2（Ovol 2）是一种锌指转录因子，是间充质-上皮转化（MET）驱动因子，其诱导前列腺癌、乳腺癌和肝细胞癌中miR-200的表达。然而，很少有人知道MET在肉瘤中的表达和功能，包括OS。本研究探讨了Ovol 2的表达和临床病理意义及其对MET在OS中的作用。Ovol 2在OS患者的肿瘤样品中的表达进行了检查，使用免疫组织化学（IHC）。然后我们上调Ovol 2在MG-63和SW 1353细胞中的表达，检测MET相关蛋白的表达，并分别使用Cell Counting Kit-8、transwell侵袭和鬼笔环肽染色法观察Ovol 2对OS细胞增殖、迁移和细胞骨架重组的影响。在MG-63和SW 1353细胞中使用荧光素酶基因报告基因测定和在人OS组织样品中使用IHC评估锌指E盒结合同源盒1（ZEB 1）和Ovol 2之间的相关性。Ovol 2蛋白的过表达与OS的临床分级（P=0.02）和复发转移（P=0.02）有关。体外实验结果表明，Ovol 2过表达可抑制细胞的迁移和侵袭，并可调节MET相关蛋白的表达水平。Ovol 2通过与ZEB 1启动子结合抑制ZEB 1表达。Ovol 2伴随着人OS组织中ZEB 1的MHC表达减少。Ovol 2表达与OS细胞中的MET相关，并抑制ZEB 1表达和OS进展。
Osteosarcoma (OS) is the most common type of primary solid bone tumor. Ovo-like zinc finger 2 (Ovol2), a zinc finger transcription factor, is a mesenchymal–epithelial transition (MET) driver that induces miR-200 expression in prostate cancer, breast cancer, and hepatocellular carcinoma. However, little is known about the expression and function of MET in sarcomas, including OS. This study investigated the expression and clinicopathological significance of Ovol2 and its effect on MET in OS. The Ovol2 expression in the tumor samples from patients with OS was examined using immunohistochemistry (IHC). We then upregulated the Ovol2 expression in MG-63 and SW1353 cells, detected the expression of MET-associated proteins, and observed the effects of Ovol2 on OS cell proliferation, migration, and cytoskeleton reorganization using Cell Counting Kit-8, transwell invasion, and phalloidin dyeing assays, respectively. The correlation between zinc finger E-box-binding homeobox 1 (ZEB1) and Ovol2 was assessed using the luciferase gene reporter assay in the MG-63 and SW1353 cells and IHC in the human OS tissue samples. The Ovol2 protein overexpression was related to the clinical grade (P=0.02) and the recurrence and metastasis (P=0.02) of OS. Results of the in vitro experiments showed that Ovol2 overexpression can suppress cell migration and invasion and can regulate the expression levels of MET-associated proteins. Ovol2 suppresses ZEB1 expression by binding to the ZEB1 promoter. Ovol2 is concomitant with a reduced IHC expression of ZEB1 in human OS tissues. Ovol2 expression is associated with MET in OS cells and suppresses ZEB1 expression and OS progression.