Epigenome analysis of Sorafenib-resistant huh7 cell lines
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ABSTRACT:
PROVIDER: PRJNA877200 | ENA |
REPOSITORIES: ENA
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Project description:Genome-wide DNA methylation profiling of 3 Sorafenib-resistant huh7 cell lines. The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from cell lines
2024-08-28 | GSE212750 | GEO
Project description:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, and acquired resistance to sorafenib—the first-line targeted therapy for advanced HCC—remains a major clinical challenge. To investigate the molecular mechanisms underlying sorafenib resistance in HCC, we established sorafenib-resistant sublines of HepG2 and Huh7 cells through continuous exposure to increasing concentrations of sorafenib. We then performed RNA-seq analysis comparing these resistant sublines with their parental sensitive counterparts. Differential gene expression analysis revealed distinct transcriptional signatures associated with sorafenib resistance. Our findings provide a comprehensive transcriptomic resource for understanding sorafenib resistance mechanisms and identify potential candidate genes that may serve as biomarkers or therapeutic targets for overcoming drug resistance in HCC.
2026-06-10 | GSE322742 | GEO
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of lncRNAs expression profile in sorafenib resistant hepatocellular carcinoma cells. We identified 1240 differentially expressed lncRNAs with 576 up-regulated and 664 down-regulated (fold change > 2, P < 0.05) in sorafenib-resistant (HUH7-S) HCC cells (fold change > 2, P < 0.05) in sorafenib-resistant (HepG2-S) HCC cells, compared to parental sorafenib-sensitive (HUH7, HepG2) HCC cells by high-throughput sequencing. In addition, based on GO (Gene Ontology) term enrichment analysis, these differentially expressed lncRNAs are mainly related to binding and catalytic activity and biological regulation of metabolic processes in both the Huh7-S and HepG2-S cell lines compared to parental cell lines. Moreover, the differentially expressed genes analyzed by KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway were significantly related to tight junction. Among them, TCONS_00284048 and TCONS_00006019 expression were consistently up-regulated in resistant HCC cells, whereas both of them knock down increased the sensitivity of Huh7-S and HepG2-S cells to sorafenib.
2020-02-02 | GSE140202 | GEO
Project description:Hepatocellular carcinoma (HCC) is often diagnosed in patients with advanced disease who are ineligible for curative surgical therapies. Sorafenib, a multi-kinase inhibitor, is currently the only approved drug used in treating such patients. However, patients rapidly become unresponsive due to inherent and acquired drug resistance. To better understand the molecular mechanisms underlying sorafenib resistance in HCC at a global level in an unbiased manner, we conducted gene expression analysis using in vitro models of HCC sorafenib resistance using the Huh7 cell line, including a resistant pool of cells and a specific clone derived from the resistant pool.
2019-09-01 | GSE94550 | GEO
Project description:Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. Furthermore, the majority of patients become resistant to sorafenib. Recently, computational methods for drug repurposing have shown great promise to accelerate the discovery of new uses for existing drugs. In order to identify novel drugs for use against sorafenib resistant (SR)-HCC, we employed a transcriptomics-based drug repurposing method termed connectivity mapping. We conducted a comprehensive analysis of available in vitro and in vivo gene signatures of (SR)-HCC, and generated our own in vitro model using the Huh7 HCC cell line. We compared coverage of SR-HCC gene signatures across seven patient-derived HCC gene expression datasets, and observed that patients harboring the Huh7 SR-HCC gene signature had significantly reduced survival. Utilizing the Huh7 SR-HCC gene signature, we applied connectivity mapping to drug-induced gene expression profiles (n= 3,740 drugs) in the HepG2 HCC cell line from the LINCS database in order to find drugs that could oppose sorafenib resistance. We validated the use of two non-receptor tyrosine kinase inhibitors, dasatinib and fostamatinib, to reduce viability of sorafenib-resistant HCC cells and confirmed up-regulated activity of Src family kinases, the targets of dasatinib, in our SR-HCC models. We prospectively validated predicted gene expression changes in fostamatinib treated Huh7-SR via RNA-seq analysis.
2019-09-01 | GSE113005 | GEO
Project description:To delineate the transcriptomic changes induced by AD80 relative to sorafenib, we performed RNA-sequencing (RNA-seq) on HUH7 and THLE5B cells treated for 24 hours with either DMSO, sorafenib, or AD80 near respective growth inhibitory GI50 values. HUH7 cells were plated in 6 well plates, treated for 24 hrs with 0.1% DMSO, 5 µM sorafenib, and 50 nM AD80. Cells were collected in “RNAlater”, a RNA storage buffer, and RNA was collected same day using the Qiagen RNeasy mini kit.
2019-08-02 | E-MTAB-7847 | biostudies-arrayexpress
Project description:Transcriptional profiling of sorafenib-resistant and parental sensitive HepG2 and Huh7 hepatocellular carcinoma cells
| PRJNA1431396 | ENA
Project description:sorafenib is the treatment of reference for hepatocellular carcinoma (HCC). We applied sorafenib on the human HCC cell line Huh7 and the subclone shRb, carrying a stable knock-down of the expression of the RB1 gene, a key regulator of liver carcinogenesis. Our aim was to better understand the physiologic and metabolic consequences of the exposure of HCC cells to sorafenib. We used microarrays to detail the global programme of gene expression at an early time point (9h) after exposure to sorafenib Whole-genome microarrays were used to study the transcriptome of Huh7 cells exposed to Sorafenib
2016-06-30 | E-GEOD-75620 | biostudies-arrayexpress
Project description:To investigate the molecular mechanism of ferroptosis resistance in HCC, we applied sorafenib, one of the class I ferroptosis inducers (FINs), to generate HepG2 sorafenib resistant (SR) cells.
2024-02-03 | GSE248764 | GEO
Project description:OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in 2 independent cohorts. RESULTS: Sorafenib-acquired resistance tumors showed significant enrichment of T-ICs (164 cells needed to create a tumor) vs. sorafenib-sensitive tumors (13400 cells) and non-treated tumors (1292 cells), p<0.001. Tumors with sorafenib-acquired resistance were enriched with IGF and FGF signaling cascades (FDR<0.05). In vitro, cells derived from sorafenib-acquired resistant tumors and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumor growth and improved survival in sorafenib-resistant tumors. A sorafenib-resistance 175-gene signature was characterized by enrichment of progenitor-cell features, aggressive tumoral traits and predicted poor survival in 2 cohorts (n=442 HCC patients). CONCLUSION: Acquired resistance to sorafenib is driven by tumor initiating cells with enrichment of progenitor markers and activation of IGF and FGF signaling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression. Transcriptomic profile of subcutaneous Huh7 cells-derived tumors treated with sorafenib that developed acquired resistance to the drug (n=4), remain responsive to sorafenib (n=3) or were treated with brivanib after development of resistance (n=3). Gene profiling of hepatospheres generated from tumors with acquired resistance to sorafenib (n=3) and non-treated tumors (n=3) was also analyzed.
2016-06-16 | E-GEOD-73571 | biostudies-arrayexpress