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 language | English |
|---|---|
| Article number | 12284 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2018 |
| Externally published | Yes |
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Cite this
MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma. / 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.
In: Scientific Reports, Vol. 8, No. 1, 12284, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
AU - Hung, Jung Hsien
AU - Li, Chung Hsien
AU - Yeh, Ching Hua
AU - Huang, Pin Cheng
AU - Fang, Cheng Chieh
AU - Chen, Yen Fu
AU - Lee, Kuo Jui
AU - Chou, Chih Hung
AU - Cheng, Hsin Yun
AU - Huang, Hsien Da
AU - Chen, Marcelo
AU - Tsai, Ting Fen
AU - Lin, Anya Maan Yuh
AU - Yen, Chia Hung
AU - Tsou, Ann Ping
AU - Tyan, Yu Chang
AU - Chen, Yi Ming Arthur
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85051737006&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051737006&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-30682-5
DO - 10.1038/s41598-018-30682-5
M3 - Article
AN - SCOPUS:85051737006
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 12284
ER -