Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma

Pan, Zhipeng; Bao, Yawei; Hu, Mengyao; Zhu, Yue; Tan, Chaisheng; Fan, Lulu; Yu, Han; Wang, Anqi; Cui, Jie; Sun, Guoping

doi:10.1038/s41420-023-01355-8

Cited by 31 publications

(15 citation statements)

References 48 publications

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“…Research has demonstrated that HSP90AA1 can modulate the expression of autophagy-related proteins, including cathepsin and LC3, thereby promoting autophagy [28]. Moreover, HSP90AA1 exerts antioxidant effects by neutralizing free radical production and reducing oxidative stress-induced damage to myocardial cells [29]. Studies have shown that HSP90AA1 can enhance the activity of antioxidant enzymes, incorporating enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), consequently resulting in a decrease in levels of oxidative stress [29,30].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

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Background: Myocardial ischemia is a prevalent cardiovascular disease with a high incidence and mortality rate. Restoring blood flow to the ischemic myocardium as soon as possible is crucial for improving patients' prognosis, but this process can lead to myocardial ischemia-reperfusion injury (MIRI). Mitophagy is a specific cellular autophagic process that has been consistently linked to various cardiovascular disorders.Nevertheless, the connection between ischemia-reperfusion and mitophagy remains unclear. This study's objective is to discern and substantiate central mitophagy-related genes associated with MIRI through bioinformatics analysis. Methods: The microarray expression profile dataset (GSE108940) was obtained from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using GEO2R. These DEGs were then cross-referenced with genes in the mitophagy database. Differential nucleotide sequence analysis used enrichment analysis.The DEGs were obtained through protein-protein interaction (PPI)network analysis. And the hub genes were clustered by cytoHubba and MCODE of Cytoscape software. GSEA analysis was conducted on central genes. Finally, we conducted Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses to corroborate the expression patterns of pivotal genes in MIRI-afflicted rats. Results: 2719 DEGs and 61 mitophagy-DEGs were obtained,followed by enrichment analyses and construction of PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1,HIF-1α and BNIP3 were the 7 hub genes identified by cytoHubba and MCODE of Cytoscape software. The functional clustering score of HIF-1α and BNIP3 was 9.647 by analysis of Cytoscape (MCODE). In our constructed MIRI rat model, western blot and immunofluorescence confirmed a significant elevation in the expression of HIF-1α and BNIP3, along with a significant increase in the ratio of LC3II to LC3I. Finally,qPCR confirmed that expression of HIF-1α, BNIP3 and LC3 mRNA in MIRI group was elevated significantly. Conclusions: Seven central genes among the mitophagy-related DEGs have been pinpointed, potentially holding pivotal significance in MIRI, which indicated that HIF-1α/BNIP3 pathway of mitophag was correlated with pathogenesis of MIRI. Mitophagy may play an important role in MIRI.This research will offer valuable insights into the underlying mechanisms and potential therapeutic targets, which can be explored in future studies.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

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“…Notably, N-Acetyltransferase 10 (NAT10), the only nuclear protein with lysine acetyltransferase activity, increased acetylation status after the treatment in the glycolytic cell line. This protein has been related to the cell cycle and promotes tumor metastasis [ 44 ]. Interestingly, the auto-acetylation of NAT10 at K426 is required to activate rRNA transcription [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes

Fernández-Coto,

Gil,

Ayala

et al. 2024

IJMS

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Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome’s functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two glioblastoma cell lines, each exhibiting distinct metabolic behaviors, following the chemical inhibition of SIRT3. Our findings reveal that the protein synthesis machinery, regulated by lysine acetylation, significantly influences the metabolic phenotype of these cells. Moreover, we have shed light on potential novel SIRT3 targets, thereby unveiling new avenues for future investigations. This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.

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“…Research has demonstrated that HSP90AA1 can modulate the expression of autophagy-related proteins, including cathepsin and LC3, thereby promoting autophagy [ 29 ]. Moreover, HSP90AA1 exerts antioxidant effects by neutralizing free radical production and reducing oxidative stress-induced damage to myocardial cells [ 30 ]. Studies have shown that HSP90AA1 can enhance the activity of antioxidant enzymes, incorporating enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), consequently resulting in a decrease in levels of oxidative stress [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

Chen,

Liu,

Yuan

et al. 2024

BMC Cardiovasc Disord

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Background Myocardial ischemia is a prevalent cardiovascular disorder associated with significant morbidity and mortality. While prompt restoration of blood flow is essential for improving patient outcomes, the subsequent reperfusion process can result in myocardial ischemia–reperfusion injury (MIRI). Mitophagy, a specialized autophagic mechanism, has consistently been implicated in various cardiovascular disorders. However, the specific connection between ischemia–reperfusion and mitophagy remains elusive. This study aims to elucidate and validate central mitophagy-related genes associated with MIRI through comprehensive bioinformatics analysis. Methods We acquired the microarray expression profile dataset (GSE108940) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using GEO2R. Subsequently, these DEGs were cross-referenced with the mitophagy database, and differential nucleotide sequence analysis was performed through enrichment analysis. Protein–protein interaction (PPI) network analysis was employed to identify hub genes, followed by clustering of these hub genes using cytoHubba and MCODE within Cytoscape software. Gene set enrichment analysis (GSEA) was conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes. Results A total of 2719 DEGs and 61 mitophagy-DEGs were identified, followed by enrichment analyses and the construction of a PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1, HIF-1α, and BNIP3 emerged as the seven hub genes identified by cytoHubba and MCODE of Cytoscape software. Functional clustering analysis of HIF-1α and BNIP3 yielded a score of 9.647, as determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation in the expression of HIF-1α and BNIP3, accompanied by a notable increase in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-1α, BNIP3, and LC3 mRNA in the MIRI group. Activation of the HIF-1α/BNIP3 pathway mediates the regulation of the degree of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes. Conclusions This study has identified seven central genes among mitophagy-related DEGs that may play a pivotal role in MIRI, suggesting a correlation between the HIF-1α/BNIP3 pathway of mitophagy and the pathogenesis of MIRI. The findings highlight the potential importance of mitophagy in MIRI and provide valuable insights into underlying mechanisms and potential therapeutic targets for further exploration in future studies.

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Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma

Cited by 31 publications

References 48 publications

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

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