hepatitis b virus x protein up-regulates akr1c1 expression through nuclear factor-y in human hepatocarcinoma cells
نویسندگان
چکیده
background the hepatitis b virus x (hbx) protein has long been recognized as an important transcriptional transactivator of several genes. human aldo-keto reductase family 1, member c1 (akr1c1), a member of the family of akr1cs, is significantly increased in hbx-expressed cells. objectives this study aimed to investigate the possible mechanism of hbx in regulating akr1c1 expression in hepg2.2.15 cells and the role of akr1c1 for hbv-induced hcc. materials and methods rt-pcr was performed to detect akr1c1 expression on mrna level in hepg2 and hepg2.2.15 cell. the promoter activity of akr1c1 was assayed by transient transfection and dual-luciferase reporter assay system. the akr1c1 promoter sequence was screened using the tfsearch database and the alibaba 2.0 software. the potential transcription factors binding sites were identified using 5’ functional deletion analysis and site-directed mutagenesis. results in this study, we found that hbx promoted akr1c1 expression in hepg2.2.15 cells. knockdown of hbx inhibited akr1c1 activation. the role of hbx expression in regulating the promoter activity of human akr1c1 gene was analyzed. the 5’functional deletion analysis identified that the region between -128 and -88 was the minimal promoter region of hbx to activate akr1c1 gene expression. site-directed mutagenesis studies suggested that nuclear factor-y (nf-y) plays an important role in this hbx-induced akr1c1 activation. conclusions in hepg2.2.1.5 cell, hbx can promote akr1c1 promoter activity and thus activates the basal transcription of akr1c1 gene. this process is mediated by the transcription factor nf-y. this study explored the mechanism for the regulation of hbv on akr1c1 expression and has provided a new understanding of hbv-induced hcc.
منابع مشابه
Hepatitis B Virus X Protein Up-Regulates AKR1C1 Expression Through Nuclear Factor-Y in Human Hepatocarcinoma Cells
BACKGROUND The hepatitis B virus X (HBx) protein has long been recognized as an important transcriptional transactivator of several genes. Human aldo-keto reductase family 1, member C1 (AKR1C1), a member of the family of AKR1CS, is significantly increased in HBx-expressed cells. OBJECTIVES This study aimed to investigate the possible mechanism of HBx in regulating AKR1C1 expression in HepG2.2...
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عنوان ژورنال:
hepatitis monthlyجلد ۱۳، شماره ۵، صفحات ۰-۰
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