Cargando…

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

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 plas...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095880/
https://www.ncbi.nlm.nih.gov/pubmed/30115977
http://dx.doi.org/10.1038/s41598-018-30682-5
_version_ 1783348000665370624
author 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
author_facet 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
author_sort Hung, Jung-Hsien
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6095880
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-60958802018-08-20 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 Sci Rep Article 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. Nature Publishing Group UK 2018-08-16 /pmc/articles/PMC6095880/ /pubmed/30115977 http://dx.doi.org/10.1038/s41598-018-30682-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
title MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
title_full MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
title_fullStr MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
title_full_unstemmed MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
title_short MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma
title_sort microrna-224 down-regulates glycine n-methyltransferase gene expression in hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095880/
https://www.ncbi.nlm.nih.gov/pubmed/30115977
http://dx.doi.org/10.1038/s41598-018-30682-5
work_keys_str_mv AT hungjunghsien microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT lichunghsien microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT yehchinghua microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT huangpincheng microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT fangchengchieh microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT chenyenfu microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT leekuojui microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT chouchihhung microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT chenghsinyun microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT huanghsienda microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT chenmarcelo microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT tsaitingfen microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT linanyamaanyuh microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT yenchiahung microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT tsouannping microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT tyanyuchang microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma
AT chenyimingarthur microrna224downregulatesglycinenmethyltransferasegeneexpressioninhepatocellularcarcinoma