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

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12 Citations (Scopus)

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 languageEnglish
Article number12284
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • General

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