MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma.

Abstract

Glycine N-methyltransferase (GNMT) is a tumor suppressor for HCC. It is down-regulated in HCC, but the mechanism is not fully understood. MicroRNA-224 (miR-224) acts as an onco-miR in HCC. This study is the first to investigate miR-224 targeting the coding region of GNMT transcript. The GNMT-MT plasmid containing a miR-224 binding site silent mutation of the GNMT coding sequence can escape the suppression of miR-224 in HEK293T cells. Expression of both exogenous and endogenous GNMT was suppressed by miR-224, while miR-224 inhibitor enhanced GNMT expression. miR-224 counteracts the effects of GNMT on the reduction of cell proliferation and tumor growth. The levels of miR-224 and GNMT mRNA showed a significant inverse relationship in tumor specimens from HCC patients. Utilizing CCl4-treated hepatoma cells and mice as a cell damage of inflammatory or liver injury model, we observed that the decreased expression levels of GNMT were accompanied with the elevated expression levels of miR-224 in hepatoma cells and mouse liver. Finally, hepatic AAV-mediated GNMT also reduced CCl4-induced miR-224 expression and liver fibrosis. These results indicated that AAV-mediated GNMT has potential liver protection activity. miR-224 can target the GNMT mRNA coding sequence and plays an important role in GNMT suppression during liver tumorigenesis.

• Authors: Jung-Hsien Hung, Chung-Hsien Li, Ching-Hua Yeh, Pin-Cheng Huang, Cheng-Chieh Fang, Yen-Fu Chen, Kuo-Jui Lee, Chih-Hung Chou, Hsin-Yun Cheng, Hsien-Da Huang, Marcelo Chen, Ting-Fen Tsai, Anya Maan-Yuh Lin, Chia-Hung Yen, Ann-Ping Tsou, Yu-Chang Tyan, Yi-Ming Arthur Chen
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 12284 (08 16 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30115977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• MIRN224 microRNA, human
• MicroRNAs
• RNA, Messenger
• Acyltransferases
• glycine acyltransferase

Topics

• 3' Untranslated Regions
• Acyltransferases (genetics)
• Animals
• Carcinoma, Hepatocellular (enzymology, genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Down-Regulation (physiology)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• Liver Neoplasms (enzymology, genetics)
• Mice
• Mice, Transgenic
• MicroRNAs (genetics, physiology)
• RNA, Messenger (genetics)