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

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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.
Original languageAmerican English
Article number12284
JournalScientific Reports
Volume8
DOIs
StatePublished - 16 Aug 2018

Keywords

  • CARBON-TETRACHLORIDE; MICROARRAY ANALYSIS; CHRONIC HEPATITIS; MIR-224; MIRNA; IDENTIFICATION; DEFICIENCY; PATHWAY; GNMT; HEPATOTOXICITY

Fingerprint Dive into the research topics of 'MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma'. Together they form a unique fingerprint.

Cite this