MiR-199a-5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma.

Abstract

The deregulation of microRNA (miRNA) is frequently associated with a variety of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the expression and possible role of miR-199a-5p in HCC. The expression of miR-199a-5p was measured by quantitative RT-PCR in HCC. The effect of miR-199a-5p was evaluated by cell viability and colony formation assays in HCC cell lines and tumor cell growth assay in xenograft nude mice. Quantitative real time PCR results showed that miR-199a-5p was down-regulated in 77.9 % (67/86) of HCC tissues compared with adjacent nontumor tissues. MiR-199a-5p mimic reduced cell viability and colony formation by induction of cell arrest in HCC cell lines and inhibited tumor cell growth in xenograft nude mice, but miR-199a-5p inhibitor increased cell viability and colony formation in HCC cell lines and tumor cell growth in xenograft nude mice. Furthermore, CLTC was defined as a potential direct target of miR-199a-5p by MiRanda and TargetScan predictions. The dual-luciferase reporter gene assay results showed that CLTC was a direct target of miR-199a-5p. The use of miR-199a-5p mimic or inhibitor could decrease or increase CLTC protein levels in HCC cell lines. We conclude that the frequently down-regulated miR-199a-5p can regulate CLTC and might function as a tumor suppressor in HCC. Therefore, miR-199a-5p may serve as a useful therapeutic agent for miRNA-based HCC therapy.

• Authors: Guo-Hao Huang, Hong Shan, Dan Li, Bin Zhou, Peng-Fei Pang
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 35 Issue 2 Pg. 98-104 (Mar 2017) ISSN: 1099-0844 [Electronic] England
• PMID: 28261837 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 John Wiley & Sons, Ltd.

Chemical References

• CLTC protein, human
• MicroRNAs
• mirn199 microRNA, human
• Clathrin Heavy Chains
• Luciferases

Topics

• Aged
• Animals
• Carcinogenesis (genetics, metabolism, pathology)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Clathrin Heavy Chains (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Humans
• Liver Neoplasms (genetics, metabolism, pathology)
• Luciferases (genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Neoplasm Transplantation
• Signal Transduction