MicroRNA-6126 downregulates NTCP expression through decreasing stability of its messenger RNA in hepatocyte
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE180543 | GEO | 2022/08/01
REPOSITORIES: GEO
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Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection. Transcriptome profiling by DNA microarray of Huh7.5.1 cells transduced to express NTCP.
2016-10-25 | E-GEOD-79089 | biostudies-arrayexpress
Project description:Aim: Hepatitis B virus (HBV) infection is one of the most serious global health problems. Our previous study revealed that an increase in the miR-6126 serum level over one year of pegylated interferon therapy predicted a decrease in hepatitis B surface (HBs) antigens. We aimed to clarify whether miR-6126 downregulated the expression level of sodium taurocholate cotransporting polypeptide (NTCP), a host cell receptor required for HBV entry. Methods: HepG2-NTCP and PXB cells were utilized to evaluate the expression level of NTCP after transfection with miR-6126. The protein expression level of NTCP was evaluated using Western blot analysis and immunostaining. The expression profile of messenger RNAs was evaluated using next-generation sequencing to search for direct targets of miR-6126.
2021-12-28 | GSE192617 | GEO
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.
2016-10-25 | GSE79089 | GEO
Project description:Chronic hepatitis B virus (HBV) infections represent a significant global health burden requiring effective therapeutic interventions. This study investigates the antiviral potential of microRNAs (miRNAs) targeting the HBV entry receptor, sodium-taurocholate cotransporting polypeptide (NTCP). Using an interferon (IFN) alpha analog, we highlighted a set of miRNAs induced in treated human hepatocytes. Notably, miR-29b-1-5p was predicted to interact with the 3’-untranslated region (3’-UTR) of NTCP. Functional analysis revealed that miR-29b-1-5p directly targeted and inhibited NTCP. Furthermore, miR-29b-1-5p overexpression significantly reduced HBV genome levels in infected hepatocytes. A rescue experiment demonstrated that miR-29b-1-5p antiviral effect was specifically mediated by NTCP targeting. In summary, these findings underscore the therapeutic potential of miR-29b-1-5p against HBV, advocating for the exploration of miRNA-based therapies in the treatment of human viral infections.
2024-04-26 | GSE264652 | GEO
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acids-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acids uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acids metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.
2016-10-25 | GSE85091 | GEO
Project description:Chronic hepatitis B virus (HBV) infections remain a health burden affecting ~250 million people worldwide. Thus far, available interferon-alpha (IFNα)-based therapies have shown unsatisfactory cure rates, and alternative therapeutic molecules are still required. However, their development has been hampered because accessible cell models supporting relevant HBV replication and appropriate antiviral activity are lacking. Strategies that reverse epigenetic alterations offer a unique opportunity for cell reprogramming, which is valuable for restoring altered cellular functions in human cell lines. This work aimed to investigate the feasibility of converting HepG2 cells that stably overexpress the HBV entry receptor (sodium/taurocholate cotransporting polypeptide, NTCP) toward IFNα-responsive cells using epigenetic reprogramming. Herein, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine restored the anti-HBV action of IFNα in epigenetically reprogrammed HepG2-NTCP-C4 cells, named REP-HepG2-NTCP cells. Thus, a significant inhibition in HBV DNA levels was measured in REP-HepG2-NTCP cells after IFNα treatment. This inhibitory effect was associated with the enhancement of IFNα-mediated induction of critical interferon-stimulated genes (ISGs), which was limited in non-reprogrammed cells. In particular, our data indicated that re-expression of 2’-5’-oligoadenylate synthetase 1 (OAS1) and interferon regulatory factor 9 (IRF9) was the result of an epigenetically driven unmasking of these genes in reprogrammed cells. At last, we evaluated the therapeutic potential of the IFN analog CDM-3008 in REP-HepG2-NTCP cells and demonstrated the efficiency of this chemical compound in triggering ISG induction and HBV inhibition. In summary, this study shows that epigenetic reprogramming promotes the IFNα response in HBV-infected cells and is potentially attractive for cell-based experimental screening of IFN-like compounds.
2020-11-24 | GSE160648 | GEO
Project description:Background and Aims: To verify the protective effect of Ezetimibe, an sodium taurocholate co-transporting polypeptide (NTCP) inhibitor, on α-amanitin poisoning in vitro and in vivo by inhibiting NTCP to prevent α-amanitin into hepatocytes. Approach and Results: In animal experiments, the survival rate was significantly improved in the treatment group. The pathomorphological characteristics of liver and kidney in the treatment group were significantly improved. In cell experiments,The cell viability of the treatment group was significantly improved, and the expression of NTCP in the treatment group was significantly decreased by immunofluorescence. In molecular docking simulations, we demonstrated the potential of NTCP to bind Ezetimibe and α-amanitin, respectively. Transcriptomics in high-throughput sequencing was used to detect the differential metabolic genes between α-amanitin poisoning group and the treatment group, and signal pathway enrichment was used to analyze the significantly different signal pathways. Conclusions: Ezetimibe, as an inhibitor of NTCP, can reduce the entry of α-amanitin into hepatocytes to play a protective role and improve the cell viability and survival rate of mice.
2023-06-30 | GSE235740 | GEO
Project description:Examination of interferon stimulated genes treated with different kind of interferon subtypes in HBV-infected HepG2-NTCP cells.
2020-04-20 | GSE138567 | GEO
Project description:Microarray data to compare the gene expression in HepG2-NTCP and Huh-106 cell lines Knowledge of HBV virus-host interactions is still limited. Here, we performed a genome-wide gain-of-function screen using weakly permissive Huh-106 cells to uncover novel HBV host factors.
2020-04-21 | GSE132638 | GEO
Project description:Impaired bile flow (cholestasis) leads to transcriptional downregulation of the bile acid importer Na+-taurocholate co-transporting protein (NTCP) and to ER-stress in the liver. Here, we show that ER-stress induction strongly reduces NTCP protein expression, plasma membrane abundance and NTCP-mediated bile acid uptake. This is not controlled via a single specific UPR-pathway but mainly depends on the interaction of NTCP with calnexin, an ER chaperone involved in folding of N-glycosylated proteins. In mice, expression of both Ntcp and calnexin was reduced by thapsigargin-induced ER-stress. Calnexin downregulation in HepG2 and U2OS cells results in a decreased NTCP expression and a reduced bile acid uptake. Calreticulin shows partial functional redundancy with calnexin as it also interacts with NTCP, and is downregulated upon ER-stress, but specifically in calnexin-depleted cells. In conclusion, ER stress-induced downregulation of calnexin provides an additional mechanism to dampen NTCP-mediated bile acid uptake during cholestasis.
2019-01-07 | PXD007948 | Pride