標題: MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
作者: Hung, Jung-Hsien
Li, Chung-Hsien
Yeh, Ching-Hua
Huang, Pin-Cheng
Fang, Cheng-Chieh
Chen, Yen-Fu
Lee, Kuo-Jui
Chou, Chih-Hung
Cheng, Hsin-Yun
Huang, Hsien-Da
Chen, Marcelo
Tsai, Ting-Fen
Lin, Anya Maan-Yuh
Yen, Chia-Hung
Tsou, Ann-Ping
Tyan, Yu-Chang
Chen, Yi-Ming Arthur
生物科技學系
生物資訊及系統生物研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
公開日期: 16-Aug-2018
摘要: 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.
URI: http://dx.doi.org/10.1038/s41598-018-30682-5
http://hdl.handle.net/11536/148017
ISSN: 2045-2322
DOI: 10.1038/s41598-018-30682-5
期刊: SCIENTIFIC REPORTS
Volume: 8
Appears in Collections:Articles