{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:33:59Z","timestamp":1777480439355,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CBM"],"published-print":{"date-parts":[[2021,9,24]]},"abstract":"<jats:p>BACKGROUND: 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. METHODS: 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. RESULTS: 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-\u03b21 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. CONCLUSION: 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.<\/jats:p>","DOI":"10.3233\/cbm-203169","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T13:43:30Z","timestamp":1622555010000},"page":"137-146","source":"Crossref","is-referenced-by-count":8,"title":["Epigenetically-regulated serum GAS5 as a potential biomarker for patients with chronic hepatitis B virus infection"],"prefix":"10.1177","volume":"32","author":[{"given":"Yong","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxue","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yating","family":"Zhan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinglu","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Department of Laboratory Medicine, Lishui Municipal Central Hospital, Lishui, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfu","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/CBM-203169_ref1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/S0140-6736(15)61412-X","article-title":"Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013","volume":"386","author":"Schweitzer","year":"2015","journal-title":"Lancet"},{"key":"10.3233\/CBM-203169_ref2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00430-014-0380-z","article-title":"Antiviral therapy for chronic hepatitis B in China","volume":"204","author":"Zheng","year":"2015","journal-title":"Med Microbiol Immunol"},{"key":"10.3233\/CBM-203169_ref3","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1053\/jhep.2000.16602","article-title":"Practices of liver biopsy in France: results of a prospective nationwide survey. 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