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Histone lactylation drives liver cancer metastasis by facilitating NSF1 mediated ferroptosis resistance after microwave ablation

ABSTRACT: Histone lactylation drives liver cancer metastasis by facilitating NSF1 mediated ferroptosis resistance after microwave ablation

PROVIDER: PRJNA1173544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31013100_1.fastq.gz	Fastqsanger.gz
	SRR31013100_2.fastq.gz	Fastqsanger.gz
	SRR31013101_1.fastq.gz	Fastqsanger.gz
	SRR31013101_2.fastq.gz	Fastqsanger.gz
	SRR31013102_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Histone lactylation drives liver cancer metastasis by facilitating NSF1 mediated ferroptosis resistance after microwave ablation

Project description:Insufficient microwave ablation (IMWA) is linked to aggressive hepatocellular carcinoma (HCC) progression. An increase in lactate level after sublethal heat stress (HS) has been confirmed in HCC. However, the role of lactate-related histone lactylation in the progression of HCC underwent sublethal HS remains unclear. Here, we found that the metastatic potential of HCC is enhanced in a lactate-dependent manner after IMWA. Meanwhile, sublethal HS triggers an upregulation of H3K18la modification, as validated in a cell-derived xenograft mouse model and human HCC samples. By employing an integration analysis of proteomic and transcriptomic profiling, we revealed that HCC cells exhibit an upregulation of intracellular iron ion homeostasis and develop resistance to platinum-based drugs after exposure to sublethal HS. We subsequently integrated proteomic and transcriptomic data with H3K18la-specific chromatin immunoprecipitation (ChIP) sequencing to identify candidate genes involved in sublethal heat treatment-induced HCC cell metastasis. Mechanically, the upregulation of H3K18la modification enhances the transcriptional activity of NFS1, a key player in iron-sulfur clusters biosynthesis, thereby reducing the susceptibility of HCC to ferroptosis post IMWA. Knocking down NFS1 diminished the metastatic potential of sublethal heat-treated HCC cell. Additionally, the deficiency of NFS1 exhibited a synergistic effect with oxaliplatin, leading to a significant inhibition of the metastatic capability of HCC cells both in vitro and in vivo, regardless of HS treatment. In conclusion, our study reveals the oncogenic role of Histone lactylation in HCC after IMVA, we also bridge histone lactylation with ferroptosis, which provides novel therapeutic targets for HCC following microwave ablation, particularly when combined with oxaliplatin-based chemotherapy.

2025-03-12 | GSE279569 | GEO

Histone lactylation drives liver cancer metastasis by facilitating NSF1-mediated ferroptosis resistance after microwave ablation.

Project description:Insufficient microwave ablation (IMWA) is linked to aggressive hepatocellular carcinoma (HCC) progression. An increase in lactate levels after sublethal heat stress (HS) has been confirmed in HCC. However, the role of lactate-related histone lactylation in the progression of HCC caused by sublethal HS remains unclear. Here, we found that the metastatic potential of HCC increased in a lactate-dependent manner after IMWA. Moreover, sublethal HS triggered an increase in H3K18la modification, as validated in a cell-derived xenograft mouse model and human HCC samples. By performing an integrated analysis of proteomic and transcriptomic profiles, we revealed that HCC cells exhibited increased intracellular iron ion homeostasis and developed resistance to platinum-based drugs after exposure to sublethal HS. We subsequently integrated proteomic and transcriptomic data with H3K18la-specific chromatin immunoprecipitation (ChIP) sequencing to identify candidate genes involved in sublethal heat treatment-induced HCC cell metastasis. Mechanically, an increase in H3K18la modification enhanced the transcriptional activity of NFS1 cysteine desulfurase (NFS1), a key player in iron‒sulfur cluster biosynthesis, thereby reducing the susceptibility of HCC to ferroptosis after IMWA. Knocking down NFS1 diminished the metastatic potential of sublethally heat-treated HCC cells. Additionally, NFS1 deficiency exhibited a synergistic effect with oxaliplatin, leading to the significant inhibition of the metastatic capability of HCC cells both in vitro and in vivo, regardless of sublethal HS treatment. In conclusion, our study revealed the oncogenic role of histone lactylation in HCC after IMVA. We also bridged histone lactylation with ferroptosis, providing novel therapeutic targets for HCC following microwave ablation, particularly when combined with oxaliplatin-based chemotherapy.

| S-EPMC11876915 | biostudies-literature

GCLM lactylation mediated by ACAT2 promotes ferroptosis resistance in KRASG12D-mutant cancer

Project description:KRAS mutation activates multiple intracellular signalling pathways, leading to tumour development and progression. However, whether KRAS mutations are involved in regulating ferroptosis in cancer and the underlying mechanism remains unclear. Here, we constructed stable KRASWT and KRASG12D-mutant cell lines by transfecting wild-type (WT) or G12D plasmids into original KRAS WT cells and detected their cell viability under the treatment of ferroptosis inducer RSL3 or erastin. We found compared with WT cells, KRASG12D-mutated pancreatic and colorectal cancer cells presented greater viability and less cell death, along with lower levels of lipid peroxidation (LPO) and fewer damaged mitochondria, suggesting that the G12D mutation confers resistance to ferroptosis. Moreover, we found that KRASG12D mutated cancer cells demonstrated increased glycolysis and elevated lactate production, which was dependent on MEK-ERK-mediated L-lactate dehydrogenase A (LDHA) phosphorylation. Importantly, lactate supplementation in WT cells also resulted in ferroptosis resistance, indicating that G12D mutation-induced resistance to ferroptosis may be linked to lactate production. Mechanistically, G12D mutation-derived lactate accumulation induces Glutamate-cysteine ligase modifier (GCLM) lactylation, a process catalysed by Acetyl-CoA Acetyltransferase 2 (ACAT2). Inhibition of GCLM lactylation either through the mutation of the lactylation site or by knockdown of ACAT2 diminished the enzymatic activity of Glutamate-cysteine ligase (GCL) and suppressed Glutathione (GSH) synthesis. Ultimately, we found that ACAT2 knockdown can overcomes ferroptosis resistance in G12D-mutated cancer models in vivo. Thus, our study reveals a novel role for the G12D mutation in regulating GCLM lactylation and ferroptosis. Targeting GCLM lactylation may represent a promising strategy for overcoming ferroptosis resistance.

2025-05-07 | PXD062451 | Pride

Histone lactylation drives endothelial activation-mediated lung injury in sepsis-associated ARDS via promoting ferroptosis

Project description:The activation of pulmonary endothelial cells (ECs) triggers the occurrence of lung injury and is a hallmark of sepsis-associated acute respiratory distress syndrome(ARDS). Aberrant metabolism favoring glycolysis plays a pivotal role in the pathogenesis of sepsis-induced EC activation. Herein we demonstrate that glycolysis-related histone lactylation, represented by H3K14 lactylation (H3K14la), drives sepsis-associated EC activation and lung injury. Accordingly, H3K14la level is elevated in injured lung tissue and activated ECs. Inhibition of lactate production suppresses both H3K14la levels and EC activation in response to lipopolysaccharide (LPS). We also show that lactate-dependent H3K14la is enriched at the promoters of ferroptosis-related genes, thereby inducing ferroptosis in ECs, and inhibiting ferroptosis effectively ameliorates EC activation. Taken together, elevated lactate in sepsis modulates EC activation and lung injury via histone lactylation and manipulation of glycolysis/H3K14la/ferroptosis axis may provide novel therapeutic approaches for the treatment of sepsis-associated ARDS.

2023-01-01 | GSE212087 | GEO

TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation against Cancer

Project description:TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation against Cancer

| PRJNA799733 | ENA

TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation against Cancer

Project description:Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy. In this study, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups. We found that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME). In conclusion, TIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment.

2022-03-30 | GSE194209 | GEO

CIRSE Emprint Microwave Ablation Registry

Project description:Observation of the clinical use of the Emprint Microwave Ablation System for the ablation of Liver Metastases of Colorectal Adenocarcinoma.

| 2292194 | ecrin-mdr-crc

The safety and efficacy of microwave ablation and radiofrequency ablation for colorectal cancer liver metastasis : A randomized controlled clinical trial

Project description:Interventions: Microwave ablation Radiofrequency ablation Primary outcome(s): The primary endpoint is the Modified RECIST evaluated by the CT scan taken after the first session of microwave ablation or radiofrequency ablation. Study Design: Parallel Randomized

| 2651257 | ecrin-mdr-crc

Interfering with glycolysis potentiates the long-term effect of local tumor ablation via CD8+TCM cell differentiation [MWA+PBS or MWA+2DG]

Project description:To evaluate the genetic changes of systemic CD8+T cells induced by microwave ablation(MWA+PBS) or microwave ablation combined with 2DG(MWA+2DG),We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different spleens from two group of mice.

2024-05-04 | GSE245637 | GEO

Interfering with glycolysis potentiates the long-term effect of local tumor ablation via CD8+TCM cell differentiation [MWA or MWA+2DG group]

Project description:To evaluate the immune responses in tumor-draining lymph nodes induced by microwave ablation (MWA) or microwave ablation combined with 2DG (MWA+2DG), we then performed gene expression profiling analysis using data obtained from RNA-seq of 5 different lymph nodes from two group of mice.

2024-05-04 | GSE222600 | GEO

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