Versican 3'-untranslated region (3'-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity.

Abstract

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.

• Authors: Ling Fang, William W Du, Xiangling Yang, Kui Chen, Anand Ghanekar, Gary Levy, Weining Yang, Albert J Yee, Wei-Yang Lu, Jim W Xuan, Zhongli Gao, Feng Xie, Chengyan He, Zhaoqun Deng, Burton B Yang
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 27 Issue 3 Pg. 907-19 (Mar 2013) ISSN: 1530-6860 [Electronic] United States
• PMID: 23180826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• MicroRNAs
• Neoplasm Proteins
• Protein Isoforms
• RNA, Neoplasm
• VCAN protein, human
• Vcan protein, mouse
• Versicans

Topics

• 3' Untranslated Regions
• Animals
• Apoptosis (genetics)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Endothelial Cells (metabolism, pathology)
• Hep G2 Cells
• Humans
• Liver Neoplasms (genetics, metabolism, pathology)
• Mice
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Proteins (biosynthesis, genetics)
• Protein Isoforms (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Versicans (biosynthesis, genetics)