MicroRNA expression profile in response to CDM-3008 treatment in human hepatocytes.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1103747 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Oral administration of nucleotide analogues and injection of interferon-alpha (IFNalpha) are used to achieve immediate suppression in replication of hepatitis B virus (HBV). Nucleotide analogs and IFNalpha inhibit viral polymerase activity and cause long-term eradication of the virus at least in part through removing covalently closed circular DNA (cccDNA) via induction of the APOBEC3 deaminases family of molecules, respectively. This study aimed to explore whether the orally administrable low molecular weight agent CDM-3008 (RO8191), which mimics IFNalpha through the binding to IFNalpha receptor 2 (IFNAR2) and the activation of the JAK/STAT pathway, can suppress HBV replication and reduce cccDNA levels. In primary cultured human hepatocytes, HBV DNA levels as well as cccDNA levels were decreased after CDM-3008-treatment in a dose-dependent manner with a half-maximal inhibitory concentration (IC50) value of 0.1 micro M, and this was accompanied by significant reductions in both HBeAg and HBsAg levels in the cell culture medium. Using a microarray we comprehensively analyzed and compared changes in gene (mRNA) expression in CDM-3008- and IFNalpha-treated primary cultured human hepatocytes. As reported previously, CDM-3008 mimicked the induction of molecules that participate in the interferon signaling pathway. OAS1 and ISG20 mRNA expression was similarly enhanced by both CDM-3008 and IFNalpha. Thus, CDM-3008 could suppress pgRNA expression to show anti-HBV activity. APOBEC3F and 3G mRNA expression was induced by CDM-3008 and IFNalpha treatment suggesting that cccDNA could be degraded through induced APOBEC3 family proteins. Finally, we identified the genes whose expression was specifically enhanced in CDM-3008-treated cells compared to IFNalpha-treated cells. The expression of SOCS1, SOCS2, SOCS3, and CISH, which inhibit STAT activation, was enhanced in CDM-3008-treated cells suggesting that a feedback inhibition of the JAK/STAT pathway was enhanced in CDM-3008-treated cells compared to IFNalpha-treated cells. In addition, CDM-3008 showed an additive effect with entecavir on inhibition of HBV replication. In summary, CDM-3008 showed anti-HBV activity through activation of the JAK/STAT pathway, inducing the expression of interferon-stimulated genes (ISGs), with greater feedback inhibition than IFNalpha.
2019-02-06 | GSE126090 | 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:An interferon-like small chemical compound CDM-3008 suppresses hepatitis B virus through induction of interferon-stimulated genes
| PRJNA521001 | ENA
Project description:Comparison of the Streptococcus pneumoniae D39 wild-type in CDM Plus 0mM CO and CDM plus 0,5 mM Co
2015-07-13 | GSE57696 | GEO
Project description:Background & Aims: IFN-alpha and -gamma have been reported to suppress cccDNA via APOBEC3 cytidine deaminase activity, and CDM-3008, an IFNAR2 agonist, also suppress cccDNA through interferon signaling. In order to develop a novel anti-HBV drug for functional or complete cure, we performed in silico screening using a structure of CDM-3008-binding pocket in IFNAR2. Approach & Results: The binding pocket of CDM-3008 in IFNAR2 was determined by LC-MS/MS using a CDM-3008-based molecular probe, CDM-3095 and a recombinant protein of IFNAR2 extracellular region. We conducted in silico screening of the binding compounds fitting the steric structure of the pocket. We identified 37 compounds and named them iCDM-1–37. We found that iCDM-34 showed anti-HCV and anti-HBV activities. We measured the anti-HBV activity of iCDM-34 with or without entecavir (ETV). iCDM-34 suppressed pregenome RNA, covalently closed circular DNA (cccDNA), HBsAg, and HBeAg and clearly exhibited synergistic inhibitory effects with ETV. Metabolic stability of iCDM-34 was measured in human, mouse, and rat microsomal fractions. iCDM-34 was stable in human liver microsomal fraction. Furthermore, anti-HBV activity in human hepatocyte-chimeric mice revealed that iCDM-34 was not effective as a single agent, but when combined with ETV, it suppressed HBV DNA and cccDNA compared to ETV alone. Phosphoproteome analysis showed no activation of IFN signaling with iCDM-34 treatment. Transcriptome analysis of interferon-stimulated genes (ISGs) revealed no increase in the expression, while downstream factors of aryl hydrocarbon receptor (AhR) showed increased expression. Conclusion: iCDM-34 is a novel anti-HBV drug that induces AhR activation and suppresses cccDNA. Conclusion: iCDM-34 is a novel anti-HBV drug that induces AhR activation and suppresses cccDNA.
2022-03-25 | GSE180646 | GEO
Project description:Berberine, an isoquinoline alkaloid isolated from many medicinal herbs such as Coptis chinensis, has a wide range of pharmacological effects. Since xenobiotic drug-induced micoRNAs have recently emerged as key regulators in guiding their pharmacological effects and toxicity, we were interested in whether or not micoRNA expression was differentially altered by berberine treatment in liver. Here, we used miRNA microarray to analyze microRNA expression profiles of primary human hepatocytes after berberine chloride treatment or 0.08% DMSO as control. Comparing miRNA profiles of 40 ïM berberine-treated primary human hepatocytes to those of control cells sampled after 2 hours treatment. A 50 mM stock solution of Berberine chloride was prepared in DMSO. Cells were treated with 40 ïM berberine chloride or 0.08% DMSO as control.
2015-12-31 | E-GEOD-53413 | biostudies-arrayexpress
Project description:Berberine, an isoquinoline alkaloid isolated from many medicinal herbs such as Coptis chinensis, has a wide range of pharmacological effects. Since xenobiotic drug-induced micoRNAs have recently emerged as key regulators in guiding their pharmacological effects and toxicity, we were interested in whether or not micoRNA expression was differentially altered by berberine treatment in liver. Here, we used miRNA microarray to analyze microRNA expression profiles of primary human hepatocytes after berberine chloride treatment or 0.08% DMSO as control.
2015-12-31 | GSE53413 | GEO
Project description:Human primary hepatocytes isolated from chimeric mice were infected with HBV for 7 days. The comprehensive changes of miRNA levels were determined by miRNA array. MicroRNA expression levels were compared in between control and HBV-replicating primary hepatocytes by 2K microRNA microarrays
2014-03-15 | E-GEOD-55929 | biostudies-arrayexpress
Project description:Escherichia coli strain:B-3008 Genome sequencing
| PRJNA933640 | ENA
Project description:We determined the microRNA expression profiles of the hepatocytes and liver sinusoidal endothelial cells (LSECs) isolated from nontreated rats.
2017-12-11 | GSE97229 | GEO