煤气5
甲基化
生物标志物
DNA甲基化
肝星状细胞
癌症研究
下调和上调
甲基转移酶
医学
长非编码RNA
生物
免疫学
内科学
基因表达
基因
生物化学
作者
Yong Guo,Chunxue Li,Rongrong Zhang,Yating Zhan,Jinpeng Yu,Jinfu Tu,Jianjian Zheng
出处
期刊:Cancer Biomarkers
[IOS Press]
日期:2021-09-24
卷期号:32 (2): 137-146
被引量:4
摘要
Long non-coding RNA-growth arrest specific transcript 5 (lncRNA-GAS5) plays a suppressive role in activated hepatic stellate cells (HSCs). LncRNAs could circulate in the blood in a cell-free form and serve as promising biomarkers for various human diseases. Herein, we investigated the feasibility of using serum GAS5 as a biomarker for liver fibrosis in chronic hepatitis B (CHB) patients and whether promoter methylation was responsible for GAS5 down-regulation.Serum GAS5 levels were quantified using quantitative real-time PCR in CHB patients and healthy controls. GAS5 promoter methylation was examined in LX-2 cells and cirrhotic tissues.Compared with the sera from healthy controls, lower GAS5 levels were found in the sera from CHB patients. Receiver operating characteristic curve analysis indicated that serum GAS5 had a significant diagnostic value for liver fibrosis in CHB patients. Serum GAS5 negatively correlated with HAI scores as well as ALT values in CHB patients. GAS5 was additionally reduced in cirrhotic tissues, associated with its hypermethylation promoter. In LX-2 cells, transforming growth factor-β1 treatment led to a reduction in GAS5 expression and an increase in promoter methylation. Hypermethylation of GAS5 was blocked down by DNA methyltransferase (DNMT) inhibitor and restored GAS5 inhibited HSC activation including proliferation and collagen production. Further studies confirmed that GAS5 methylation was mediated by DNMT1.We demonstrate that epigenetically-regulated serum GAS5 could serve as a potential biomarker in CHB patients. Loss of GAS5 is associated with DNMT1-mediated promoter methylation.
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