Background/Aims: This study aimed to investigate the microRNA (miRNA) expression profiles in peripheral blood mononuclear cell (PBMC) of hepatitis B virus (HBV)-infected patients with different clinical manifestations and to analyze the function of miR-197. Methods: PBMC miRNA expression profiles in 51 healthy controls, 70 chronic asymptomatic carriers, 107 chronic hepatitis B patients, and 76 HBV-related acute on chronic liver failure patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). miR-197 mimic and inhibitor were transfected in THP-1 cells. qRT-PCR and ELISA for interleukin (IL)-18 mRNA and protein levels were performed, respectively. Results: The microarray analysis revealed that 17 PBMC miRNA expression profiles (12 miRNAs downregulated and five miRNAs upregulated) differed significantly in HBV-induced liver disease patients presenting with various symptoms. The qRT-PCR results suggested that the PBMC miR-197 levels regularly decreased as the severity of liver disease symptoms became aggravated. IL-18, a key regulator in inflammation and immunity, was inversely correlated with miR-197 levels. Bioinformatic analysis indicated that IL-18 was a target of miR-197. Exogenous expression of miR-197 could significantly repress IL-18 expression at both the mRNA and protein levels in THP-1 cells. Conclusions: We concluded that multiple PBMC miRNAs had differential expression profiles during HBV infection and that miR-197 may play an important role in the reactivation of liver inflammation by targeting IL-18.
机构:
Mem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, CanadaMem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, Canada
MacParland, Sonya A.
Corkum, Christopher P.
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Mem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, CanadaMem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, Canada
Corkum, Christopher P.
Burgess, Christopher
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Novartis Oncol Compan Diagnost, Cambridge, MA 02139 USAMem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, Canada
Burgess, Christopher
Karwowska, Sylwia
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Novartis Oncol Compan Diagnost, Cambridge, MA 02139 USAMem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, Canada
Karwowska, Sylwia
Kroll, Werner
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Novartis Oncol Compan Diagnost, Cambridge, MA 02139 USAMem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, Canada
Kroll, Werner
Michalak, Tomasz I.
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Mem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, CanadaMem Univ Newfoundland, Fac Med, Mol Virol & Hepatol Res Grp, Div BioMed Sci,Hlth Sci Ctr, St John, NF A1B 3V6, Canada
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Assiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USAAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Sayed, Ibrahim M.
Abd Elhameed, Zeinab A.
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Assiut Univ, Dept Clin Pathol, Fac Med, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Abd Elhameed, Zeinab A.
Abd El-Kareem, Doaa M.
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Assiut Univ, Dept Clin Pathol, Fac Med, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Abd El-Kareem, Doaa M.
Abdel-Malek, Mohamed A. Y.
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Assiut Univ, Dept Clin Pathol, Fac Med, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Abdel-Malek, Mohamed A. Y.
Ali, Mohamed E.
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Al Azhar Univ, Fac Pharm, Dept Microbiol & Immunol, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Ali, Mohamed E.
Ibrahim, Maggie A.
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Assiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Ibrahim, Maggie A.
Sayed, Ayat Abdel-Rahman
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Assiut Univ, Fac Med, Dept Med Biochem, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Sayed, Ayat Abdel-Rahman
Khalaf, Khaled Abo Bakr
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Assiut Univ, Fac Med, Dept Trop Med & Gastroenterol, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Khalaf, Khaled Abo Bakr
Abdel-Wahid, Lobna
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Assiut Univ, Fac Med, Dept Internal Med, Gastroenterol & Hepatol Unit, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Abdel-Wahid, Lobna
El-Mokhtar, Mohamed A.
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Assiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt
Sphinx Univ, Fac Pharm, Microbiol & Immunol Dept, Assiut, EgyptAssiut Univ, Fac Med, Dept Med Microbiol & Immunol, Assiut, Egypt