hepatitis b virus x protein up-regulates akr1c1 expression through nuclear factor-y in human hepatocarcinoma cells

نویسندگان

kai li department of molecular biology on infectious disease, second affiliated hospital, chongqing medical university, chongqing, china

shijia ding department of clinical laboratory diagnostics, chongqing medical university, chongqing, china

ke chen department of molecular biology on infectious disease, second affiliated hospital, chongqing medical university, chongqing, china

dongdong qin department of molecular biology on infectious disease, second affiliated hospital, chongqing medical university, chongqing, china

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.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

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...

متن کامل

The hepatitis B virus X protein up-regulates lymphotoxin alpha expression in hepatocytes.

Hepatitis B virus X protein (HBx) is involved in intrahepatic inflammatory processes by inducing several pro-inflammatory cytokines. It has been suggested that these inflammatory processes play an important role in causing hepatocarcinogenesis. In this study, we investigated the role of HBx in the expression of lymphotoxin alpha (LTalpha) in hepatoma cells such as Huh-7 and Chang. Our experimen...

متن کامل

Hyperbaric environment up-regulates CD15s expression on leukocytes, down-regulates CD77 expression on renal cells and up-regulates CD34 expression on pulmonary and cardiac cells in rat

Objective(s): The aim of this study was to estimate effects of hyperbaric (HB) treatment by determination of CD15s and CD11b leukocyte proinflammatory markers expression.  In addition, this study describes changes in CD77 and CD34 expression on rat endothelial cells in renal, pulmonary and cardiac tissue following exposure to hyperbaric pressure. Materials and Methods:Expression of CD11b and CD...

متن کامل

Hepatitis B virus X protein up-regulates C4b-binding protein α through activating transcription factor Sp1 in protection of hepatoma cells from complement attack

Hepatitis B virus X protein (HBx) plays crucial roles in the development of hepatocellular carcinoma (HCC). We previously showed that HBx protected hepatoma cells from complement attack by activation of CD59. Moreover, in this study we found that HBx protected hepatoma cells from complement attack by activation of C4b-binding protein α (C4BPα), a potent inhibitor of complement system. We observ...

متن کامل

In Silico Prediction and Docking of Tertiary Structure of Multifunctional Protein X of Hepatitis B Virus

Hepatitis B virus (HBV) infection is a universal health problem and may result into acute, fulminant, chronic hepatitis liver cirrhosis, or hepatocellular carcinoma. Sequence for protein X of HBV was retrieved from Uniprot database. ProtParam from ExPAsy server was used to investigate the physicochemical properties of the protein. Homology modeling was carried out using Phyre2 server, and refin...

متن کامل

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1.

We investigated the effects of the hepatitis B virus X gene (HBV X) on the activation of human hepatic stellate cells (HSCs) and the possible mechanisms underlying the pathway. Recombinant plasmid pHBV-X-IRES2-EGFP was constructed and transfected into HL-7702 cells using a lipid-mediated method. Transfected cells were screened by G418, which detected stable expression of the X gene by reverse t...

متن کامل

منابع من

با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید


عنوان ژورنال:
hepatitis monthly

جلد ۱۳، شماره ۵، صفحات ۰-۰

میزبانی شده توسط پلتفرم ابری doprax.com

copyright © 2015-2023