Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1130017 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RNA-seq data for parental and lenvatinib-resistant HCC (Hep3B, Huh7) cells
2022-03-23 | GSE186191 | GEO
Project description:Lenvatinib is a multiple receptor tyrosine kinases inhibitor (TKI) authorized for first-line treatment of hepatocellular carcinoma (HCC). However, Lenvatinib resistance is common in HCC clinical treatment, highlighting the urgent need to understand mechanisms of resistance. Here, we identified Golgi membrane protein 1 (GOLM1), a type II transmembrane protein originally located in the Golgi apparatus, as a novel regulator of Lenvatinib resistance. We established Lenvatinib resistance in human HCC cell lines PLC/PRF/5. Through RNA-seq, we found that GOLM1 was significantly upregulated, which was further validated in patients derived tumor tissue and peripheral blood. GOLM1 overexpression contributes to Lenvatinib resistance and HCC progression in vitro and in vivo. Mechanistically, GOLM1 upregulates CSN5 expression through EGFR-STAT3 pathway. Reversely, CSN5 deubiquitinates and stabilizes GOLM1 protein by inhibiting ubiquitin-proteasome pathway of GOLM1. Collectively, our data demonstrate that GOLM1 is one of the key driver of Lenvatinib resistance in HCC and depicts a molecular network in Lenvatininb resistant HCC cells.
2024-08-07 | GSE273819 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis is a form of chronic liver inflammation associated with metabolic syndrome, such as obesity and a major cause of hepatocellular carcinoma. Multi-biotics, a soymilk fermented with lactic acid bacteria, are known to alleviate obesity by lowering lipid profile. In this study, we investigated efficacy of multi-biotics in MASH-related HCC using mouse model fed choline-deficient L-amino acid-defined high-fat diet, and determined that tumor regression was not affected by multi-biotics. We established mouse MASH-related HCC organoids, and performed RNA-sequencing to identify transcriptomic features in MASH-HCC treated multi-biotics. We also examined response of MASH-related HCC to four HCC treatment drugs, and MASH-related HCC treated multi-biotics was good response to Lenvatinib. We established Lenvatinib-resistant MASH-related HCC organoids by administrating repeatedly Lenvatinib, and identified enriched pathways in Lenvatinib-resistant models. This study provides a tool for studying MASH-related HCC treatment and Lenvatinib resistance by establishing the MASH-related HCC and Lenvatinib resistance organoid model.
2024-10-17 | GSE272024 | GEO
Project description:RNA-seq data for parental and lenvatinib-resistant HCC cells
| PRJNA772933 | ENA
Project description:Using a kinome-centred CRISPR/Cas9 genetic screen, we identify here that inhibition of the epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer cells. We found that the combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effect in HCC cell lines that express EGFR in vitro and of xenografted HCC cell lines or patient-derived HCC tumours in mice. Herre, we analyzed the different transcriptome profiling of HCC cells treated with DMSO, lenvatinib, gefitinib, and lenvatinib plus gefitinib by RNA-sequencing.
2021-07-22 | GSE157905 | GEO
Project description:To determine the drug target of lenvatinib, RNAseq was used to evaluate the transcriptome differences between lenvatinib-treated MHCC-97H cells and their parental counterparts.Results show that SERPINE1 may be direct target of lenvatinib, and AKR1C1 have potential prognostic significance in the prediction of LR(lenvatinib-resistant) in HCC. AKR1C1 could be a promising therapeutic target for patients with LR-type liver cancer.
2022-11-01 | GSE214324 | GEO
Project description:Lenvatinib is the FDA-approved targeted drug for advanced hepatocellular carcinoma (HCC), but the efficacy is modest due to drug resistance. Tumor kinome re-wiring governs drug resistance in resistant cancer cells, which is an obstacle for efficient cancer therapy. Therefore, identification the kinases critical for this rewiring process in HCC is crucial.This study reveals the new role of CDK6 and its mechanistic insight in regulation of cancer stemness and drug resistance. These results support the combination treatment of lenvatinib with palbociclib for advanced HCC patients. Further studies will optimize patient target selection and identify the best treatment combinations.
2023-09-29 | PXD038152 | Pride
Project description:To investigate the mechanism of lenvatinib resistance, we established the lenvatinib resistant Huh7 (Huh7 LR) cells by continuous exposuring to lenvatinib (1–20 μM) for approximately 10 months. We then performed gene expression profiling analysis using data obtained from RNA-seq of Huh7 parental (Huh7 P) cells and the lenvatinib resistant Huh7 (Huh7 LR) cells.
2022-08-26 | GSE211850 | GEO
Project description:Lenvatinib targets multiple oncogenic kinases including vascular endothelial growth factor receptors (VEGFRs) and showed longer median progression-free survival than sorafenib, the only approved treatment for >10 years. With the successful combination therapy of anti-PD-L1 pembrolizumab and anti-VEGF bevacizumab for advanced HCC as well as encouraging experimental findings, lenvatinib was also expected to enhance anti-tumor effects by combining anti-PD-1 pembrolizumab compared to lenvatinib alone; however, the phase III clinical trial failed to show their synergetic survival benefits, highlighting the need for elucidating its mode of action in human HCC specimens after lenvatinib treatment. We performed multi-layer transcriptome analyses of surgically resected human HCC samples after lenvatinib treatment as a neo-adjuvant therapy using RNA-sequencing. Molecular pathway analyses and immunohistochemistry revealed that VEGF-mediated aberrant vascularity and cytotoxic GZMK+CD8 T cells infiltration were significantly improved in lenvatinib-treated HCC; however, the majority of these cytotoxic T cells were trapped in the intratumor fibrotic stroma, suggesting that lenvatinib-treated HCC is in the so-called excluded condition. Excluded tumors are generally believed to be less responsive to immune checkpoint inhibitors, which might be the reason the combination therapy failed to show the additive benefits.
2023-08-08 | GSE223201 | GEO