Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protein expression signature in cell competition in HCC

ABSTRACT: Although increasing studies have proved cell competition widely involved in the growth and homeostasis of multicellular organisms is closely linked to tumorigenesis and development, the mechanistic contributions between drug resistance and tumor cell competition remain ill-defined. In this paper, we applied MS of cell competition group to determine the dominant characteristics of lenvatinib resistance and its metabolic differences in cell competition. Our results showed a vital role of HSP90-IDH1 mediated lipid accumulation in maintaining the competitive outcome of HCC drug-resistant cells via regulating lipid metabolism. HSP90-IDH1 axis could be a promising target to overcome HCC drug resistance.

ORGANISM(S): Homo Sapiens

SUBMITTER: Sikai Wang

PROVIDER: PXD046294 | iProX | Fri Oct 20 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

Exosomal circRNA-MANBA mediates sorafenib resistance of hepatocellular carcinoma via miR-1290/CD109/p-STAT3 (Ser727) axis

Project description:Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions. Our study aims to explore the novel mechanisms by which exosome-contained circRNAs promote sorafenib resistance in hepatocellular carcinoma (HCC). Here we report that a circular RNA, circRNA-MANBA (a circular RNA upregulated in exosomes derived from sorafenib-resistant HCC cells), plays a significant role in sorafenib resistance in HCC. We identified that circRNA-MANBA is increased in sorafenib-resistant HCC cells, their exosomes, and tumor samples from sorafenib-treated HCC patients. Depletion of circRNA-MANBA substantially increases the cell-killing ability of sorafenib. Co-culture experiments revealed that exosomes from sorafenib-resistant HCC cells carrying large amounts of circRNA-MANBA could transmit drug resistant capacity to parental cells. Further studies revealed that circRNA-MANBA acted as ‘miRNAs sponge’ to absorb miR-1290, which prevented miR-1290 interaction with CD109 and thus upregulated STAT3 phosphorylation subsequently. Using different HCC mouse models, we demonstrated that silencing circRNA-MANBA by injection of siRNA could substantially overcome sorafenib resistance. Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-MANBA.

2023-11-07 | GSE213242 | GEO

cDCBLD2 mediates sorafenib resistance in hepatocellular carcinoma by sponging miR-345-5p binding to the TOP2A coding sequence

Project description:Sorafenib is a first-line chemotherapy drug for treating advanced hepatocellular carcinoma (HCC). However, its therapeutic effect has been seriously affected by the emergence of sorafenib resistance in HCC patients. The underlying mechanism of sorafenib resistance is unclear. Here, we report a circular RNA, cDCBLD2, which plays an important role in sorafenib resistance in HCC. We found that cDCBLD2 was upregulated in sorafenib-resistant (SR) HCC cells, and knocking down cDCBLD2 expression could significantly increase sorafenib-related cytotoxicity. Further evidence showed that cDCBLD2 can bind to microRNA (miR)-345-5p through a competing endogenous RNA mechanism, increase type IIA topoisomerase (TOP2A) mRNA stability through a miRNA sponge mechanism, and reduce the effects of sorafenib treatment on HCC by inhibiting apoptosis. Our findings also suggest that miR-345-5p can negatively regulate TOP2A levels by binding to the coding sequence region of its mRNA. Additionally, targeting cDCBLD2 by injecting a specific small interfering RNA (siRNA) could significantly overcome sorafenib resistance in a patient-derived xenograft (PDX) mouse model of HCC. Taken together, our study provides a proof-of-concept for a potential strategy to overcome sorafenib resistance in HCC patients by targeting cDCBLD2 or TOP2A.

2023-12-11 | GSE240109 | GEO

Pharmacoproteomics identifies kinase pathways that drive the epithelial-mesenchymal transition and drug resistance in hepatocellular carcinoma

Project description:Hepatocellular carcinoma (HCC) is a complex and deadly disease lacking druggable genetic mutations. The limited efficacy of systemic treatments for advanced HCC implies that novel predictive biomarkers and drug targets are urgently needed. Most HCC drugs target protein kinases and their kinase-dependent signaling networks to drive HCC progression. To identify HCC signaling networks that determine responses to kinase inhibitors (KIs), we apply a pharmacoproteomics approach integrating kinome activity in 17 HCC cell lines with their responses to 299 KIs, resulting in a comprehensive dataset of pathway-based drug response signatures. By profiling patient HCC samples, we identify signatures of clinical HCC drug responses in individual tumors. Our analyses reveal kinase networks promoting the epithelial-mesenchymal transition (EMT) and drug resistance, including a FZD2-AXL-NUAK1/2 signaling module, whose inhibition reverses the EMT and sensitizes HCC cells to drugs. Our approach identifies cancer drug targets and molecular signatures of drug response for personalized oncology.

2018-12-15 | MSV000083236 | MassIVE

Lefamulin targets ILF3 to overcome targeted therapy resistance in hepatocellular carcinoma

Project description:Acquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, we identified a U.S. Food and Drug Administration (FDA)-approved pleuromutilin antibiotic that overcomes sorafenib resistance in HCC cell lines, cell line-derived xenograft (CDX) and hydrodynamic injection mouse models. We demonstrated that lefamulin targets and binds Interleukin Enhancer-binding Factor 3 (ILF3) to inhibit sorafenib-induced mitochondrial ribosomal protein L12 (MRPL12) upregulation. Mechanistically, lefamulin directly binds to Ala-99 of ILF3 and interferes with acetyltransferase general control non-depressible 5 (GCN5) and CREB binding protein (CBP) mediated acetylation of Lys-100, which disrupting the ILF3-mediated transcription of MRPL12 and subsequent mitochondrial biogenesis. Clinical data further confirmed that high ILF3 or MRPL12 expression was associated with poor survival and targeted therapy efficacy in HCC. Conclusively, our findings suggest that ILF3 is a potential therapeutic target for overcoming resistance to TKIs, and lefamulin may be a novel combination therapy strategy for HCC treatment with sorafenib and regorafenib.

2024-01-17 | GSE252988 | GEO

Lefamulin targets ILF3 to overcome targeted therapy resistance in hepatocellular carcinoma []

2024-01-17 | GSE252987 | GEO

Expression data from SOX9 knockdown in HCC cells

Project description:Sorafenib is a multi-kinase blocker and one of the few suggested drug treatments for aggressive hepatocellular carcinoma (HCC) patients. However, drug resistance to sorafenib may often occur over time and cause further tumor aggression. Recently, cancer stem cells were found in HCC and were speculated to be involved in tumor progression. SOX9 is highly expressed in HCC cancer stem cells and promotes cell proliferation and self-renewal. Meanwhile, HCC patients with higher SOX9 expression show poorer prognosis [1]. Whether SOX9 is involved in sorafenib resistance in HCC is still unclear. Here, we found that sorafenib treatment increased SOX9 expression in HCC cell lines. Overexpression of exogenous SOX9 in HCC increased sorafenib resistance both in vitro and in vivo, whereas down-regulation led to inhibition of sorafenib resistance. Knock-down of SOX9 by RNA interference caused down-regulation of downstream genes, including ATP binding cassette subfamily G member 2 (ABCG2). The drug resistance to sorafenib caused by SOX9 overexpression could be ameliorated by overexpression of SOX9 in combination withby ABCG2 inhibition in HCC cell lines. In the cohort of patients resistant to sorafenib, we found that patients with lower SOX9 expression had more prolonged overall survival (OS) and progression-free survival (PFS). Cox analysis shows that SOX9 expression exerts as an independent risk factor for HCC, and logistic regression analysis reveals that SOX9 expression, tumor capsule deficiency, tumor diameters, and microvascular invasion are risk factors for poor prognosis of HCC patients. These findings demonstrate that SOX9 enhances sorafenib resistance and may regulate this process by modulating ABCG2 expression.

2020-01-13 | GSE143477 | GEO

YAP/TAZ and ATF4 collaboratively drive resistance to Sorafenib therapy in hepatocellular carcinoma by preventing ferroptosis

Project description:Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA-mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib-induced ferroptosis. Mechanistically, in a TEAD-dependent manner YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovered a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance.

2021-08-20 | GSE181771 | GEO

Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma

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

Transcriptomics of an in vitro model of sorafenib resistance in Huh7 hepatocellular carcinoma cell line

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

Functional genomics uncovers pleiotropic role of rhomboids in C. glutamicum

Project description:The physiological role of ubiquitous rhomboid proteases, membrane-integral proteins that cleave their substrates inside the lipid bilayer, is ill-defined in prokaryotes. The two rhomboid genes cg0049 and cg2767 of Corynebacterium glutamicum were deleted and consequences investigated in respect to growth phenotype, stress resistance, transcriptome, proteome and lipidome composition.

2014-04-29 | E-MTAB-2558 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data