title: 15d-PGJ₂ decreases PGE₂ synthesis in HBx-positive liver cells by interfering EGR1 binding to mPGES-1 promoter.
abstract: Microsomal prostaglandin E synthase 1 (mPGES-1) is the terminal regulator of PGE₂ synthesis. The expression of mPGES-1 is increased by stimulating inflammatory factors in various human cancers. However, whether hepatitis B virus (HBV) infection affects mPGES-1 and its molecular mechanism in liver cells has not been studied. In this study, we observed that mPGES-1 expression was positively correlated with HBV X protein (HBx) in hepatocellular carcinoma cancerous tissue, and HBx enhanced the mPGES-1 promoter activity in HL7702 liver cells. Mechanistic investigations revealed that HBx can increase the early growth response 1 (EGR1) binding to the transcription site of mPGES-1 promoter. The overexpression and knockdown of EGR1 did not affect cyclooxygenase-2 (COX-2) transcription and expression in HL7702-HBx cells. We also investigated the unique function of 15-deoxy-Δ(12,14)-prostaglandin J₂ (15d-PGJ₂), a kind of PGE₂ inhibitor, in the regulation of mPGES-1 expression in HBx-positive liver cells. In the presence of 15d-PGJ₂, the expression of COX-2 was unaffected, but that of the EGR1-mPGES-1-PGE₂ axis was inhibited. Moreover, the capacity of EGR1 binding to the mPGES-1 promoter decreased, and the change in HL7702-HBx cells was more significant. The results indicated that EGR1 is a specific transcription factor in the up-regulation of mPGES-1 expression by HBx, and targeting EGR1 may contribute to inhibiting the change from inflammation to HBV-induced cancer.
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.
authors.forename: Siyan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou 350001, China. Electronic address: fztnh@sina.com.
authors.forename: Nanhong
authors.initials: N
authors.lastname: Tang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000821:virology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D000071876:Prostaglandin-E Synthases; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C477819:15-deoxyprostaglandin J2; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2
keywords: Early growth response 1 (EGR1); HBV X protein (HBx); Hepatocyte; Microsomal prostaglandin E synthase 1 (mPGES-1); Promoter