Transcriptomic data from a gallbladder cancer cell line with acquired chemoresistance to gemcitabine [NOZ]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA860574 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gallbladder cancer (GBC) has few therapeutic options, being gemcitabine the first-line chemotherapeutic drug. However, this treatment shows poor clinical outcomes on patients. The acquired resistance phenomenon during of the treatment is one of the main factors that leads to insufficient therapeutic effects, and the molecular mechanisms used by tumor cells against gemcitabine are still poorly understood. First, we established a GBC cell line with acquired resistance to gemcitabine (TGBC1 GemR) from parental cell line (TGBC1). After, we used microarray hybridization in TGBC1 and TGBC1 GemR to characterize their transcriptional profile to identify differentially expressed genes and/or molecular pathways involved chemoresistant cell phenotype.
2022-07-21 | GSE208660 | GEO
Project description:Gallbladder cancer (GBC) has few therapeutic options, being gemcitabine the first-line chemotherapeutic drug. However, this treatment shows poor clinical outcomes on patients. The acquired resistance phenomenon during of the treatment is one of the main factors that leads to insufficient therapeutic effects, and the molecular mechanisms carried out by tumor cells against gemcitabine are still poorly understood. First, we established a GBC cell line with acquired resistance to gemcitabine (NOZ GemR) from parental cell line (NOZ). After, we used microarray hybridization in NOZ and NOZ GemR to characterize their transcriptional profile to identify differentially expressed genes and/or molecular pathways involved chemoresistant cell phenotype.
2022-07-21 | GSE208659 | GEO
Project description:Transcriptomic data from a gallbladder cancer cell line with acquired chemoresistance to gemcitabine [TGBC1]
| PRJNA860575 | ENA
Project description:Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but unfortunately the effectiveness of any regimen is limited, and recurrence rates are high. Here, we established and characterized two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR) to investigate the molecular mechanisms associated with acquired resistance in vitro. The transcriptome profiling of parental and gemcitabine resistant cells revealed differential expression of multiple protein-coding genes and enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, quantitative phosphotyrosine proteomic analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as Abl, PDGFRA, EphB2 and members of the Src-family that could be novel therapeutic targets against drug resistance in GBC. In line with this, NOZ GemR cells showed increased sensitivity toward the multikinase inhibitor dasatinib compared with parental cells. In conclusion, our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant gallbladder cancer cells, which greatly expands our understanding of the underlying mechanisms of acquired drug-resistance in GBC. Moreover, this new gemcitabine resistant GBC models could be exploited either to study alternative mechanisms of resistance or to explore new therapies for chemotherapy-refractory GBC.
2023-05-03 | PXD036348 | Pride
Project description:Pancreatic Ductal Adenocarcinoma (PDAC) is associated with extremely poor prognosis due to late diagnosis and therapeutic resistance. Here we show that PDAC cells undergo progressive reprogramming of the global epigenetic landscape during the process of acquiring chemoresistance. Through an epigenetic inhibitor screen, we identified Protein Arginine methyltransferase 1 (PRMT1) as a central driver of chemoresistance in PDAC. Genetic or pharmacological inhibition of PRMT1 impaired adaptive epigenetic reprogramming, sensitized PDAC cells to Gemcitabine and other commonly used chemo drugs, and delayed the development of acquired resistance both in vitro and in vivo. Mechanistically, we find that PRMT1, through its enzymatic activity, limits the accumulation of small bZIP transcription factor MAFF in the nucleus, and the assembly of chromatin-bound MAFF/BACH1 hetero-oligomeric complexes following Gemcitabine treatment. Genetic silencing of MAFF heightened the resistance of PDAC cells to Gemcitabine, and to combination of Gemcitabine and PRMT1 inhibitors. Cut&Tag chromatin profiling of H3K27Ac, MAFF and BACH1 suggests a pivotal role for MAFF/BACH1 in orchestrating global epigenetic reprogramming during the course of acquiring Gemcitabine resistance. Supporting the clinical relevance of our findings, predicted PRMT1 and MAFF/BACH1 genes signatures based on our Cut&Tag analysis were able to distinguish Gemcitabine-resistant from Gemcitabine-sensitive PDAC patient-derived xenografts according to expression changes induced by Gemcitabine. Together, our study reveals a novel epigenetic regulatory axis involving PRMT1 and MAFF/BACH1 that modulates Gemcitabine response, which could be potentially exploited for improving therapeutic response in advanced PDAC.
2024-04-29 | GSE227129 | GEO
Project description:Chemotherapy resistance is a major clinical issue for pancreatic adenocarcinoma (PDAC). MicroRNAs (miRNAs) play an important role in cancer progression and chemoresistance. In this study, we addressed the association between miRNA expression profiles and gemcitabine (Gem) resistance. A Gem sensitive (GS) PDAC cancer cell line, MIA PaCa-2, and its Gem resistant (GR) progeny MIA PaCa-2 GR, was used to determine miRNA expression changes by resistance to Gemcitabine. miRNA-seq was used to determine the miRNA expression profiles in these cell lines. Ingenuity Pathway Analysis (IPA) was performed to determine the biological functions of differentially expressed miRNAs. In total, 1867 miRNAs were detected in the two cell lines. We found that the miRNA expression profiles were different between the GR and its sensitive isogenic parental GS cell line, and certain differentially expressed miRNAs were only detected in one or the other of these PDAC cell lines. A total of 97 (5.2%) miRNAs were significantly differentially expressed between GR and the GS cell lines, of which 65 (3.5%) miRNAs were upregulated and 32 (1.7%) miRNAs were downregulated. The miRNAs with the most significant differential expression in the GR cell line as compared with GS were primarily involved in the following biological processes: cell proliferation, cell migration & invasion, chemo-sensitization, alternative splicing, apoptosis, and angiogenesis. These miRNAs from cell lines were further refined to a subset and were analyzed in patient samples where expression was used to identify patients with recurrent tumors. Taken together, the results suggest that these miRNAs may play important roles in Gem resistance in PDAC. This study’s findings provides a basis for further research in the diagnosis and treatment selection for PDACs with gemcitabine resistance.
2024-07-01 | GSE269190 | GEO
Project description:miRNA signatures underly chemoresistance in the gemcitabine-resistant pancreatic ductal adenocarcinoma cell line MIA PaCa-2 GR
| PRJNA1120481 | ENA
Project description:We generated gemcitabine resistant subclones from the human pancreatic cancer cell line BxPC3 using chronic low dose exposure to gemcitabine. Three gemcitabine resistant subclones (BxGR-80C, BxGR-120C and BxGR-360C) were sequenced in addition to BxPC3 cells.
2021-12-21 | E-MTAB-11186 | biostudies-arrayexpress
Project description:Purpose: Gemcitabine is most commonly used for pancreatic cancer (PC). However, the molecular features and mechanisms of the frequently occurred resistance remain unclear. This work aims at exploring the molecular features of gemcitabine resistance and identifying candidate biomarkers and combinatorial targets for the treatment. Experimental Design: In present study, we established 66 patient-derived xenografts (PDXs) based on clinical PC specimens and treated them with gemcitabine. We generated multi-omics data (including whole exome-seq, RNA-seq, miRNA-seq and DNA methylation array) of 15 drug sensitive and 13 resistant PDXs before and after the gemcitabine treatment. We performed integrative computational analysis to identify the molecular networks related to gemcitabine intrinsic and required resistance. Then, shRNA-based high-content screening was implemented to validate the function of the de-regulated genes. Results: The comprehensive multi-omics analysis and functional experiment revealed that MRPS5 and GSPT1 had strong effects on cell proliferation, and CD55 and DHTKD1 contributed to gemcitabine resistance in PC cells. Moreover, we found miR-135a-5p was significantly associated with the prognosis of PC patients and could be a candidate biomarker to predict gemcitabine response. Comparing the molecular features before and after the treatment, we found that PI3K-Akt, p53, HIF-1 pathways were significantly altered in multiple patients, providing candidate target pathways for reducing the acquired resistance. Conclusions: This integrative genomic study systematically investigated the predictive markers and molecular mechanisms of chemoresistance in pancreatic cancer and provide potential therapy targets for overcoming gemcitabine resistance.
2021-02-09 | GSE165688 | GEO
Project description:Purpose: Gemcitabine is most commonly used for pancreatic cancer (PC). However, the molecular features and mechanisms of the frequently occurred resistance remain unclear. This work aims at exploring the molecular features of gemcitabine resistance and identifying candidate biomarkers and combinatorial targets for the treatment. Experimental Design: In present study, we established 66 patient-derived xenografts (PDXs) based on clinical PC specimens and treated them with gemcitabine. We generated multi-omics data (including whole exome-seq, RNA-seq, miRNA-seq and DNA methylation array) of 15 drug sensitive and 13 resistant PDXs before and after the gemcitabine treatment. We performed integrative computational analysis to identify the molecular networks related to gemcitabine intrinsic and required resistance. Then, shRNA-based high-content screening was implemented to validate the function of the de-regulated genes. Results: The comprehensive multi-omics analysis and functional experiment revealed that MRPS5 and GSPT1 had strong effects on cell proliferation, and CD55 and DHTKD1 contributed to gemcitabine resistance in PC cells. Moreover, we found miR-135a-5p was significantly associated with the prognosis of PC patients and could be a candidate biomarker to predict gemcitabine response. Comparing the molecular features before and after the treatment, we found that PI3K-Akt, p53, HIF-1 pathways were significantly altered in multiple patients, providing candidate target pathways for reducing the acquired resistance. Conclusions: This integrative genomic study systematically investigated the predictive markers and molecular mechanisms of chemoresistance in pancreatic cancer and provide potential therapy targets for overcoming gemcitabine resistance.
2021-02-09 | GSE165687 | GEO