Overexpression of c‐Jun inhibits erastin‐induced ferroptosis in Schwann cells and promotes repair of facial nerve function

Gao, Dedong; Huang, Yuyu; Sun, Xiayu; Yang, Jun; Chen, Jianyong; He, Jianbin

doi:10.1111/jcmm.17241

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…JUN (formally known as c-JUN), a subunit of the activator protein 1 transcription factor, has multiple roles in determining ferroptosis sensitivity through either transcription-dependent or transcription-independent mechanisms (24). It has been reported that overexpression of JUN inhibits erastin-induced ferroptosis in Schwann cells (25). JUN is also deduced as a ferroptosis suppressor in the Ferroptosis Database, which is based on the study performed on human liver cancer cells (26).…”

Section: Discussionmentioning

confidence: 99%

In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets

Yin

Zhang

et al. 2022

Front. Endocrinol.

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Type 2 diabetes (T2D) is a major global public health burden, with β-cell dysfunction a key component in its pathogenesis. However, the exact pathogenesis of β-cell dysfunction in T2D is yet to be fully elucidated. Ferroptosis, a recently discovered regulated form of non-apoptotic cell death, plays a vital role in the development of diabetes and its complications. The current study aimed to identify the key molecules involved in β-cell ferroptosis3 in patients with T2D using the mRNA expression profile data of GSE25724 by bioinformatic approaches. The differentially expressed mRNAs (DE-mRNAs) in human islets of patients with T2D were screened using the islet mRNA expression profiling data from the Gene Expression Omnibus and their intersection with ferroptosis genes was then obtained. Ferroptosis-related DE-mRNA functional and pathway enrichment analysis in T2D islet were performed. Using a protein-protein interaction (PPI) network constructed from the STRING database, Cytoscape software identified ferroptosis-related hub genes in the T2D islet with a Degree algorithm. We constructed a miRNA-hub gene network using the miRWalk database. We generated a rat model of T2D to assess the expression of hub genes. A total of 1,316 DE-mRNAs were identified in the islet of patients between T2D and non-T2D (NT2D), including 221 and 1,095 up- and down-regulated genes. Gene set enrichment analysis revealed that the ferroptosis-related gene set was significantly different in islets between T2D and NT2D at an overall level. A total of 33 ferroptosis-related DE-mRNAs were identified, most of which were significantly enriched in pathways including ferroptosis. The established PPI network with ferroptosis-related DE-mRNAs identified five hub genes (JUN, NFE2L2, ATG5, KRAS, and HSPA5), and the area under the ROC curve of these five hub genes was 0.929 in the Logistic regression model. We constructed a regulatory network of hub genes and miRNAs, and the results showed that suggesting that hsa-miR-6855-5p, hsa-miR-9985, and hsa-miR-584-5p could regulate most hub genes. In rat model of T2D, the protein expression levels of JUN and NFE2L2 in pancreatic tissues were upregulated and downregulated, respectively. These results contribute to further elucidation of ferroptosis-related molecular mechanisms in the pathogenesis of β-cell dysfunction of T2D.

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Section: Discussionmentioning

confidence: 99%

In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets

Yin

Zhang

et al. 2022

Front. Endocrinol.

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“…Some studies found that c-Jun also downregulates p53, thereby inhibiting apoptosis. Recently, a growing number of research has indicated that c-Jun participates in the regulation of ferroptosis processes in some tumors [ 47 , 48 , 49 ]. Studies have shown that c-Jun can inhibit ferroptosis by stimulating GSH synthesis by increasing PSAT1 and CBS transcription [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

Shi

Yang

Ding

et al. 2022

Biology

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Preeclampsia (PE) is the leading cause of maternal and fetal mortality and morbidity. Early and accurate diagnosis is critical to reduce mortality. Placental oxidative stress has been identified as a major pathway to the development of PE. Ferroptosis, a new form of regulated cell death, is associated with iron metabolism and oxidative stress, and has been suspected to play a role in the pathophysiology of PE, although the mechanism is yet to be elucidated. The identification of potential ferroptosis-related biomarkers is of great significance for the early diagnosis and treatment of PE. A gene expression dataset of peripheral blood samples was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially expressed genes (DEGs) were filtrated with the R package “limma”. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs were then conducted. Ferroptosis-related DEGs were screened by overlapping the ferroptosis-related genes with DEGs. The protein–protein interaction (PPI) network was used to identify the key ferroptosis-related DEGs. Enzyme-linked immunosorbent assay (ELISA) was used to validate changes in the selected key ferroptosis-related DEGs. The correlations between the key genes and clinical and pathological characteristics were analyzed. Finally, the diagnostic value of these key genes for PE was confirmed by a receiver operating characteristic (ROC) curve. A total of 5913 DEGs were identified and 45 ferroptosis-related DEGs were obtained. Besides, ferroptosis-related pathways were enriched by KEGG using DEGs. The PPI network showed that p53 and c-Jun were the critical hub genes. ELISA showed that p53 in the serum of PE patients was higher than that of the control group, while c-Jun was lower than that of the control group. Analysis of the clinicopathological features showed that p53 and c-Jun were correlated with the PE characteristics. Finally, based on the area under curve (AUC) values, c-Jun had the superior diagnostic power (AUC = 0.87, p < 0.001), followed by p53 (AUC = 0.75, p < 0.001). Our study identified that two key genes, p53 and c-Jun, might be potential diagnostic biomarkers of PE.

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“…Chang et al (2021) pointed out complex IV subunit 4 isoform 2 (Cox4i2) can trigger an increase in reactive oxygen species, leading to ferroptosis and apoptosis in human herpesvirus 7 (HHV7) infected SCs. Gao et al (2022) found the overexpression of c-Jun, a key regulator of the response of SCs to peripheral nerve injury, inhibits erastininduced ferroptosis in SCs and promotes repair of facial nerve function.…”

Section: Neuropathic Pain Induced By Peripheral Nerve Injurymentioning

confidence: 99%

“…Several SCs-related studies have tried to clarify the mechanism of ferroptosis in peripheral nerve injury ( Chang et al, 2021 ; Gao et al, 2022 ). Chang et al (2021) pointed out complex IV subunit 4 isoform 2 (Cox4i2) can trigger an increase in reactive oxygen species, leading to ferroptosis and apoptosis in human herpesvirus 7 (HHV7) infected SCs.…”

Section: Introductionmentioning

confidence: 99%

An update on the therapeutic implications of long-chain acyl-coenzyme A synthetases in nervous system diseases

Sun

et al. 2022

Front. Neurosci.

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Long-chain acyl-coenzyme A synthetases (ACSLs) are a family of CoA synthetases that activate fatty acid (FA) with chain lengths of 12–20 carbon atoms by forming the acyl-AMP derivative in an isozyme-specific manner. This family mainly includes five members (ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6), which are thought to have specific and different functions in FA metabolism and oxidative stress of mammals. Accumulating evidence shows that the dysfunction of ACSLs is likely to affect cell proliferation and lead to metabolic diseases in multiple organs and systems through different signaling pathways and molecular mechanisms. Hence, a central theme of this review is to emphasize the therapeutic implications of ACSLs in nervous system disorders.

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Overexpression of c‐Jun inhibits erastin‐induced ferroptosis in Schwann cells and promotes repair of facial nerve function

Cited by 23 publications

References 35 publications

In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets

In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

An update on the therapeutic implications of long-chain acyl-coenzyme A synthetases in nervous system diseases

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