title: MicroRNA-581 promotes hepatitis B virus surface antigen expression by targeting Dicer and EDEM1.
abstract: Hepatitis B virus surface antigen (HBsAg) is an important risk factor for hepatocellular carcinoma (HCC) and is downregulated during hepatocarcinogenesis. MicroRNAs (miRNAs) are frequently deregulated in HCC tissues. However, whether the deregulation of certain miRNAs in HCC has an impact on HBsAg expression remains unclear. We found here that microRNA-581 (miR-581), which is deregulated during hepatocarcinogenesis, promoted HBsAg expression. Additionally, miR-581 targeted Dicer and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) and repressed their expression. Although Dicer cannot process HBV transcripts, Dicer knockdown led to increased HBsAg secretion, most likely due to a reduction in the levels of Dicer-processed 7SL RNA fragments. Moreover, Dicer-processed 7SL RNA fragments partially inhibited the ability of miR-581 to stimulate HBsAg expression. Furthermore, we found that forced EDEM1 expression inhibited miR-581-mediated induction of HBsAg. Finally, transfection of miR-581 into HepG2.2.15 cells promoted cell proliferation and led to upregulation of genes involved in development, cell proliferation and protein secretion. Altogether, we conclude that miR-581 promotes HBsAg expression by targeting Dicer and EDEM1. Our findings suggest that downregulation of miR-581 during hepatocarcinogenesis may lead to a reduction in HBsAg expression and impede HCC development.
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China, Department of Infection and Liver Diseases, Liver Research Center, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, P.R. China and.
authors.forename: Yu-Qun
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Ren
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Yi-Jiang
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Xue
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China, Department of Infection and Liver Diseases, Liver Research Center, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, P.R. China and.
authors.forename: Su-Ting
authors.initials: ST
authors.lastname: Cao
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Zhu-Jun
authors.initials: ZJ
authors.lastname: Deng
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, P.R. China and.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, P.R. China and.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of the State Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of the State Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Ai-Long
authors.initials: AL
authors.lastname: Huang
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, P.R. China, tangkaifu@hotmail.com.
authors.forename: Kai-Fu
authors.initials: KF
authors.lastname: Tang
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C486654:EDEM1 protein, human; D006514:Hepatitis B Surface Antigens; C000592494:MIRN581 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases