Versican 3′-untranslated region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity
Versican 3′-untranslated region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity
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DOI：
10.1096/fj.12-220905
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发表时间：
2013-03-01
期刊：
影响因子：
4.8
通讯作者：
Yang, Burton B.
中科院分区：
文献类型：
--
作者：
Fang, Ling;Du, William W.;Yang, Burton B.
本研究旨在探讨多功能蛋白聚糖在肝细胞癌（HCC）发生发展中的作用。研究了多功能蛋白聚糖3 '-非翻译区（3'-UTR）的异位表达作为调节miRNA功能的竞争性内源RNA。我们使用这种方法来调节多功能蛋白聚糖及其相关蛋白在3 '-UTR转基因小鼠和肝癌细胞系HepG 2中的表达，所述肝癌细胞系用3'-UTR或对照载体稳定转染。我们证明了表达多功能蛋白聚糖3 '-UTR的转基因小鼠发生HCC并增加多功能蛋白聚糖亚型V0和V1的表达。转染多功能蛋白聚糖3 '-UTR的HepG 2细胞表现出增殖、存活、迁移、侵袭、集落形成增加，内皮细胞生长增强，但凋亡减少。我们发现多功能蛋白聚糖3 '-UTR可以与miRNAs miR-133 a、miR-199 a *、miR-144和miR-431结合，也可以与CD 34和纤连蛋白相互作用。因此，多功能蛋白聚糖、CD 34和纤连蛋白的表达通过多功能蛋白聚糖3 '-UTR的异位转染而上调，这在HepG 2细胞和转基因小鼠中与野生型对照相比得到证实。用靶向多功能蛋白聚糖3 '-UTR的siRNA转染消除了3'-UTR的作用。综上所述，这些结果表明，多功能蛋白聚糖V0和V1亚型在HCC的发展中起重要作用，并且多功能蛋白聚糖mRNA与内源性RNA竞争调节miRNA功能。芳湖，加-地杜，W. W.，杨，X.，陈凯，Ghanekar，A.，利维，G.，杨伟，Yee，A. J.，卢，W.-是的，Xuan，J.W.，高志，Xie，F.，他，C.，邓志，杨，B。B。Versican 3 '-非翻译区（3'-UTR）作为ceRNA通过调节miRNA活性诱导肝细胞癌的发展。FASEB J.27，907-919（2013）。www.fasebj.org
This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3'-untranslated region (3'-UTR) was studied as a competitive endogenous RNA for regulating miRNA functions. We used this approach to modulate the expression of versican and its related proteins in 3'-UTR transgenic mice and in the liver cancer cell line HepG2, stably transfected with the 3'-UTR or a control vector. We demonstrated that transgenic mice expressing the versican 3'-UTR developed HCC and increased expression of versican isoforms V0 and V1. HepG2 cells transfected with versican 3'-UTR displayed increased proliferation, survival, migration, invasion, colony formation, and enhanced endothelial cell growth, but decreased apoptosis. We found that versican 3'-UTR could bind to miRNAs miR-133a, miR-199a*, miR-144, and miR-431 and also interacted with CD34 and fibronectin. As a consequence, expression of versican, CD34, and fibronectin was up-regulated by ectopic transfection of the versican 3'-UTR, which was confirmed in HepG2 cells and in transgenic mice as compared with wild-type controls. Transfection with siRNAs targeting the versican 3'-UTR abolished the effects of the 3'-UTR. Taken together, these results demonstrate that versican V0 and V1 isoforms play important roles in HCC development and that versican mRNAs compete with endogenous RNAs in regulating miRNA functions.-Fang, L., Du, W. W., Yang, X., Chen, K., Ghanekar, A., Levy, G., Yang, W., Yee, A. J., Lu, W.-Y., Xuan, J. W., Gao, Z., Xie, F., He, C., Deng, Z., Yang, B. B. Versican 3'-untranslated region (3'-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. FASEB J. 27, 907-919 (2013). www.fasebj.org