The miR-203/SNAI2 axis regulates prostate tumor growth, migration, angiogenesis and stemness potentially by modulating GSK-3/-CATENIN signal pathway
The miR-203/SNAI2 axis regulates prostate tumor growth, migration, angiogenesis and stemness potentially by modulating GSK-3/-CATENIN signal pathway
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miR-203/SNAI2 轴通过调节 GSK-3β/β-CATENIN 信号通路潜在地调节前列腺肿瘤生长、迁移、血管生成和干性
DOI：
10.1002/iub.1720
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发表时间：
2018-03-01
期刊：
影响因子：
4.6
通讯作者：
Zhang, Zhiqian
中科院分区：
文献类型：
--
作者：
Tian, Xinxin;Tao, Fangfang;Zhang, Zhiqian
MicroRNA表达异常在包括前列腺癌在内的多种人类癌症的发生和发展中起着关键作用。我们以前的研究已经证明miR-203的沉默通过靶向SNAI2而促进了恶性乳腺癌细胞的侵袭。然而，miR-203/SNAI2轴在前列腺癌中的作用及其机制尚不清楚。本研究旨在探讨miR-203/SNAI2轴在体内外对前列腺癌生物学特性的影响。TCGA分析发现，与永生化的前列腺上皮细胞相比，miR-203在前列腺癌细胞系中的表达显著下调；在临床前列腺癌组织中，miR-203的表达也明显下调。在功能上，miR-203在体外抑制前列腺癌细胞的增殖、迁移、内皮细胞管的形成和肿瘤干细胞的形成。同时，miR-203过表达抑制了DU145和PC3细胞中SNAI2的表达。此外，体内研究表明，miR-203抑制了DU145细胞的成瘤、转移和血管生成。异位表达的SNAI2在体内和体外均挽救了miR-203的抑制作用。重要的是，EMT标志物CDH1和Vimentin受miR-203/SNAI2轴的调控。此外，GSK-3/-catenin信号通路被miR-203抑制，并可被SNAI2重新激活。综上所述，本研究揭示了miR-203/SNAI2轴在前列腺癌的发生、血管生成、干性、转移和GSK-3/-catenin信号通路中的作用，为前列腺癌患者的miR-203/SNAI2靶向治疗提供了新的思路。(C)2018年IUBMB Life，70(3)：224-236,2018
Dysregulation of microRNA expression plays a pivotal role in the initiation and progression of a variety of human carcinomas including prostate cancer. Our previous studies have demonstrated that the silence of miR-203 contributes to the invasiveness of malignant breast cancer cells by targeting SNAI2. However, the effects and underlying mechanisms of miR-203/SNAI2 axis in prostate cancer have not been elucidated. The aim of this study is to explore the effects of miR-203/SNAI2 axis on the biological characteristics of prostate carcinomas both in vitro and in vivo. We found that miR-203 was significantly downregulated in prostate cancer cell lines compared with immortalized prostate epithelial cells using semi-quantitative PCR and real-time PCR, as well as in clinical prostate cancer tissues compared to normal tissues using TCGA analysis. Functionally, miR-203 inhibited prostate cancer cell proliferation, migration, endothelial cell tube formation and cancer stemness in vitro. Meanwhile, overexpression of miR-203 suppressed SNAI2 expression both in DU145 and PC3 cells. In addition, the in vivo study showed that miR-203 suppressed tumorigenicity, metastasis and angiogenesis of DU145 cells. Ectopic expression of SNAI2 rescued the inhibitory effects of miR-203 both in vitro and in vivo. Importantly, the EMT markers CDH1 and VIMENTIN were modulated by the miR-203/SNAI2 axis. Furthermore, the GSK-3/-CATENIN signal pathway was suppressed by miR-203 and could be reactivated by SNAI2. Taken together, this research unveiled the function of miR-203/SNAI2 axis in tumorigenesis, angiogenesis, stemness, metastasis and GSK-3/-CATENIN signal pathway in prostate cancer and gave insights into miR-203/SNAI2-targeting therapy for prostate cancer patients. (c) 2018 IUBMB Life, 70(3):224-236, 2018