Exosomal circBBS2 inhibits ferroptosis by targeting miR‐494 to activate SLC7A11 signaling in ischemic stroke

Hong, Ting; Zhao, Tingting; He, Wei; Xia, Jian; Huang, Qing; Yang, Jie; Gu, Wenping; Chen, Changqing; Zhang, Ning; Liu, Yunhai; Feng, Jie

doi:10.1096/fj.202300317rrr

Cited by 17 publications

(8 citation statements)

References 43 publications

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“…Hong et al. discovered that exosomes derived from umbilical cord mesenchymal stem cells (UC-MSC) could enhance SLC7A11 expression through sponge-like miR-494, thereby inhibiting ferroptosis ( 37 ). Our analysis indicates specific expression of SLC7A11 in MSCs, suggesting that MSCs or MSC-Exo may promote tumor cell disulfidptosis by enhancing SLC7A11 expression or function, potentially offering a novel direction for effective BC treatment.…”

Section: Discussionmentioning

confidence: 99%

Impact of disulfidptosis-associated clusters on breast cancer survival rates and guiding personalized treatment

Chen,

Hu,

2023

Front. Endocrinol.

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BackgroundBreast cancer (BC) poses a serious threat to human health. Disulfidptosis is a recently discovered form of cell death associated with cancer prognosis and progression. However, the relationship between BC and disulfidptosis remains unclear.MethodsWe integrated single-cell sequencing and transcriptome sequencing in BC to assess the abundance and mutation status of disulfidptosis-associated genes (DAGs). Subsequently, we clustered the samples based on DAGs and constructed a prognostic model associated with disulfidptosis. Additionally, we performed pathway enrichment, immune response, and drug sensitivity analyses on the model. Finally, we validated the prognostic genes through Immunohistochemistry (IHC).ResultsThe single-cell analysis identified 21 cell clusters and 8 cell types. By evaluating the abundance of DAGs in different cell types, we found specific expression of the disulfidoptosis core gene SLC7A11 in mesenchymal stem cells (MSCs). Through unsupervised clustering of DAGs, we identified two clusters. Utilizing differentially expressed genes from these clusters, we selected 7 genes (AFF4, SLC7A11, IGKC, IL6ST, LIMD2, MAT2B, and SCAND1) through Cox and Lasso regression to construct a prognostic model. External validation demonstrated good prognostic prediction of our model. BC patients were stratified into two groups based on riskscore, with the high-risk group corresponding to a worse prognosis. Immune response analysis revealed higher TMB and lower TIDE scores in the high-risk group, while the low-risk group exhibited higher CTLA4/PD-1 expression. This suggests that both groups may respond to immunotherapy, necessitating further research to elucidate potential mechanisms. Drug sensitivity analysis indicated that dasatinib, docetaxel, lapatinib, methotrexate, paclitaxel, and sunitinib may have better efficacy in the low-risk group. Finally, Immunohistochemistry (IHC) validated the expression of prognostic genes, demonstrating higher levels in tumor tissue compared to normal tissue.ConclusionOur study has developed an effective disulfidptosis-related prognostic prediction tool for BC and provides personalized guidance for the clinical management and immunotherapy selection of BC patients.

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Section: Discussionmentioning

confidence: 99%

Impact of disulfidptosis-associated clusters on breast cancer survival rates and guiding personalized treatment

Chen,

Hu,

2023

Front. Endocrinol.

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“…To establish a CIRI mouse model, twelve‐week‐old male HuR −/− mice and wild‐type (WT) mice were randomly assigned to the MCAO model group and sham groups. The MCAO procedure was performed as previously described 18 …”

Section: Methodsmentioning

confidence: 99%

HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke

Wang,

Zhao,

et al. 2023

The FASEB Journal

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Human antigen R (HuR) is a universally expressed RNA‐binding protein that plays an essential role in governing the fate of mRNA transcripts. Accumulating evidence indicated that HuR is involved in the development and functions of several cell types. However, its role in cerebral ischemia/reperfusion injury (CIRI) remains unclear. In this study, we found that HuR was significantly upregulated after CIRI. Moreover, we found that silencing HuR could inhibit the inflammatory response of microglia and reduce the damage to neurons caused by oxygen–glucose deprivation/reperfusion treatment. In vivo, we found that microglial HuR deficiency significantly ameliorated CIRI and reduced NLRP3‐mediated inflammasome activation. Mechanistically, we found that HuR could regulate NLRP3 mRNA stability by binding to the AU‐rich element (ARE) region within the 3′ untranslated region (UTR) of NLRP3 mRNA. In addition, we found that the upregulation of HuR was dependent on the upregulation of NADPH oxidase‐mediated ROS accumulation. Collectively, our studies revealed that HuR could regulate NLRP3 expression and that HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke. Targeting HuR may be a novel therapeutic strategy for cerebral ischemic stroke treatment.

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“…In a rat model of cerebral I/R injury, these exosomes have shown therapeutic potential by reducing infarct size, alleviating neurological deficits, and mitigating pathological damage. This suggests that the protective effects are mediated through the regulation of ferroptosis-related pathways, offering a promising avenue for the treatment of cerebral I/R injury ( Hong et al, 2023 ).…”

Section: Exosomal Ferroptosis-related Ncrnas As Therapeuticsmentioning

confidence: 99%

Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

Zhang,

Xie

2024

Front. Cell Dev. Biol.

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Ferroptosis, an iron-dependent form of programmed cell death, introduces a novel perspective on cellular demise. This study investigates the regulatory network of exosomal non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, in ferroptosis modulation. The primary goal is to examine the pathological roles of ferroptosis-related exosomal ncRNAs, particularly in ischemic reperfusion injuries. The research reveals intricate molecular interactions governing the regulatory interplay between exosomal ncRNAs and ferroptosis, elucidating their diverse roles in different non-malignant pathological contexts. Attention is given to their impact on diseases, including cardiac, cerebral, liver, and kidney ischemic injuries, as well as lung, wound, and neuronal injuries. Beyond theoretical exploration, the study provides insights into potential therapeutic applications, emphasizing the significance of mesenchymal stem cells (MSCs)-derived exosomes. Findings underscore the pivotal role of MSC-derived exosomal ncRNAs in modulating cellular responses related to ferroptosis regulation, introducing a cutting-edge dimension. This recognition emphasizes the importance of MSC-derived exosomes as crucial mediators with broad therapeutic implications. Insights unveil promising avenues for targeted interventions, capitalizing on the diverse roles of exosomal ncRNAs, providing a comprehensive foundation for future therapeutic strategies.

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Exosomal circBBS2 inhibits ferroptosis by targeting miR‐494 to activate SLC7A11 signaling in ischemic stroke

Cited by 17 publications

References 43 publications

Impact of disulfidptosis-associated clusters on breast cancer survival rates and guiding personalized treatment

Impact of disulfidptosis-associated clusters on breast cancer survival rates and guiding personalized treatment

HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke

Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

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