@article{f1ce625d66dc42e5b58fea8ee8cce0a4,
title = "MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma",
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.",
author = "Hung, {Jung Hsien} and Li, {Chung Hsien} and Yeh, {Ching Hua} and Huang, {Pin Cheng} and Fang, {Cheng Chieh} and Chen, {Yen Fu} and Lee, {Kuo Jui} and Chou, {Chih Hung} and Cheng, {Hsin Yun} and Huang, {Hsien Da} and Marcelo Chen and Tsai, {Ting Fen} and Lin, {Anya Maan Yuh} and Yen, {Chia Hung} and Tsou, {Ann Ping} and Tyan, {Yu Chang} and Chen, {Yi Ming Arthur}",
note = "Funding Information: Specimens? from? HCC? patients.? RNA specimens were obtained from the following two groups of patients through the Taiwan Liver Cancer Network (TLCN, http://140.112.133.121/index.action): tumor and tumor-adjacent tissue pairs from 78 HCC patients (Supplementary Table S3). Five medical centers; National Taiwan University Hospital, Chang-Gung Memorial Hospitals at Linko and Kaohsiung, and Veterans General Hospitals at Taichung and Kaohsiung, participate in the TLCN. Preoperative written informed consents were obtained from all the patients recruited by the TLCN. These 78 HCC patients were subcategorized into three groups: 40 patients (20 males and 20 females) were HBsAg-positive, 20 patients (10 males and 10 females) were anti-HCV Ab-positive and 18 patients (9 males and 9 females) were negative for both HBsAg and anti-HCV antibody. The study protocol has been approved by the Institutional Review Board of the National Yang Ming University (IRB No. 1000041) and the user committee of the TLCN (No.070001 and No.120060). The clinicopathological profiles of the patients enrolled in the study are shown in Supplementary Table S3. Funding Information: This work was supported by Grant sponsor: Grants from Ministry of science and Technology (MOST) of the Republic of China: NSC99-2811-B-010–046, MOST-104–2325-B-037-002, 104–2632-B-037-001, NSC 100– 2325-B-182-006 (to TLCN). Grants from Kaohsiung Medical University “Aim for the Top 500 Universities Grant”; Grant numbers: DT103009; “Aim for the Top Universities Grant; Grant numbers: KMU-TP104E11, KMU-TP104E14, KMU-TP104D08, KMU-TP104H05, KMU-TP104A16 and KMU-DT105004. A grant from: Health and welfare surcharge of tobacco products, Ministry of Health and Welfare Grant; Grant numbers: MOHW104-TDU-B-212-124-003. Grant sponsor: National Health Research Institutes, Taiwan (to TLCN); A grant from: Center for Infectious Disease and Cancer Research, Kaohsiung Medical University: Grant numbers: KMUTP105-E08. A grant from: Kaohsiung Medical University Research Foundation; Grant numbers: 105KMUOR02 and 105KMUOR05. We thank the staff of the Center of Infectious Disease and Cancer Research (CICAR) of Kaohsiung Medical University for technical assistance. We are most grateful for Dr Ping Yueh-Hsin{\textquoteright}s gift of the psiCHECK2 plasmids.",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-30682-5",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}