Integrative analysis of ferroptosis-related genes in ulcerative colitis

Cui, Dejun; Chen, Chen; Yuan, Wenqiang; Yang, Yunhan; Han, Lu

doi:10.1177/03000605211042975

Cited by 24 publications

(20 citation statements)

References 26 publications

(29 reference statements)

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“…However, the mechanism of MUC1 in alleviating lung injury of sepsis was still unclear. In recent years, studies have shown that MUC1 was closely associated with ferroptosis and might be a biomarker related to ferroptosis [ 35 , 36 ]. Our studies indicated that inhibiting the dimerization of MUC1 could significantly reduce the expression level of GPX4, decrease the expression levels of GSH and SOD, improve MDA and MPO, increase the level of lipid peroxides, break mitochondrial membrane, and increase membrane density, thereby stimulating ferroptosis and aggravating lung injury, which proved the close relationship between MUC1 and ferroptosis in the ALI model of sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, we also found that the expression level of MUC1 (KL-6) in the plasma of sepsis patients complicated with ARDS was significantly increased and had a good predictive value for early sepsis patients complicated with ARDS [34]. Li Oxidative Medicine and Cellular Longevity in ulcerative colitis through database integration analysis [36]. However, whether MUC1 plays a role in the ferroptosis of ALI/ARDS in sepsis remains obscure, and the specific mechanism needs to be illustrated.…”

Section: Introductionmentioning

confidence: 95%

“…Li et al found that MUC1 was a ferroptosis-related gene and had an important prognostic value in idiopathic pulmonary fibrosis [ 35 ]. Cui et al identified MUC1 as a possible marker of ferroptosis in ulcerative colitis through database integration analysis [ 36 ]. However, whether MUC1 plays a role in the ferroptosis of ALI/ARDS in sepsis remains obscure, and the specific mechanism needs to be illustrated.…”

Section: Introductionmentioning

confidence: 99%

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Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3β/Keap1-Nrf2-GPX4 Pathway

Wang

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Ferroptosis is a nonapoptotic form of programmed cell death, which may be related to the occurrence and development of sepsis-induced acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). Mucin 1 (MUC1) is a kind of macromolecule transmembrane glycoprotein. Previous studies have shown that MUC1 could relieve ALI in sepsis and predict whether sepsis patients would develop into ARDS. However, the role of MUC1 in the ferroptosis of sepsis-induced ALI/ARDS remains unclear. Materials and Methods. Sera samples from 50 patients with sepsis/septic shock were used to detect iron metabolism-related markers. Western blot and qRT-PCR were conducted to detect the expression levels of ferroptosis-related genes. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factors. Transmission electron microscopy (TEM) was used to assess morphological changes of cells. Results. The results showed that the iron metabolism-related indicators in sepsis-induced ARDS patients changed significantly, suggesting the iron metabolism disorder. The expression levels of ferroptosis-related genes in lung tissues of sepsis had marked changes, and the lipid peroxidation levels increased, while Ferrostatin-1 (Fer-1) could reverse the above results, which confirmed the occurrence of ferroptosis. In terms of mechanism studies, inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3β, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. Besides, inhibiting MUC1 reversed the alleviating effect of vitamin E on ALI caused by sepsis, increased the aggregation of inflammatory cells in lung tissues, and aggravated alveolar injury and edema. Conclusions. Our study was the first to explore the changes of iron metabolism indicators in ALI/ARDS of sepsis, clarify the important role of ferroptosis in ALI/ARDS induced by sepsis, and reveal the effects and specific mechanisms of MUC1 in regulating ferroptosis, as well as the sensitization on vitamin E.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3β/Keap1-Nrf2-GPX4 Pathway

Wang

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In our previous study, we analyzed the dataset uploaded by Dunn et al using bioinformatic analyses and found that the expression of Cd44 was significantly upregulated after 7 days of carotid artery ligation ( Zhang and Gu, 2022 ). Moreover, it is closely related to ferroptosis and has been studied in ulcerative colitis ( Cui and Chen, 2021 ) and various cancers ( Liu and Jiang, 2019 ; Deng and Zheng, 2021 ; Kozawa and Sekai, 2021 ). However, the role of Cd44 in ferroptosis and IH remains unknown, this is the innovation of our research.…”

Section: Discussionmentioning

confidence: 99%

Expression profiles and functions of ferroptosis-related genes in intimal hyperplasia induced by carotid artery ligation in mice

Zhang

Shen

et al. 2022

Front. Genet.

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Intimal hyperplasia (IH) is a prominent pathological event that occurs during in-stent restenosis and atherosclerosis. Ferroptosis, characterized by iron-dependent and lipid peroxidation, has become the recent focus of studies on the occurrence and progress of cardiovascular diseases. However, there are few studies on ferroptosis and IH. Therefore, we aimed to identify and validate ferroptosis-related markers in IH to explore new possibilities for IH diagnosis and treatment. The IH microarray dataset (GSE182291) was downloaded from the Gene Expression Omnibus (GEO) database and ferroptosis-related genes (FRGs) were obtained from the FerrDb databases. The differentially expressed genes (DEGs) were analyzed using the GEO2R. Overlapping was performed to identify the ferroptosis-related DEGs among the DEGs and FRGs. Then, clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein–protein interaction (PPI) analyses were performed. Subsequently, the hub genes were identified using Cytoscape and hub gene–transcription factors and hub gene–microRNA networks were constructed. Finally, real-time qPCR (RT-qPCR) and immunohistochemistry (IHC) were used to verify the mRNA and protein levels of the hub FRGs in IH. Thirty-four FRGs showing significantly different expression were identified from a total of 1,197 DEGs 2 days after ligation; 31 FRGs were selected from a total of 1,556 DEGs 14 days after ligation. The GO and KEGG analyses revealed that these 34 ferroptosis-related DEGs identified 2 days after ligation were mainly enriched in the basolateral plasma membrane, ferroptosis, lipid and atherosclerosis, and IL-17 signaling pathways. The 31 ferroptosis-related DEGs in endometrial hyperplasia identified 14 days after ligation were mainly enriched in response to oxidative stress, ferroptosis, tumor necrosis factor signaling pathway, and lipid and atherosclerosis. Five hub FRGs (Il1b, Ptgs2, Cybb, Cd44, and Tfrc) were identified using PPI networks; four hub FRGs (Il1b, Ptgs2, Cybb, and Cd44) were validated to be upregulated 2 and 14 days after ligation using RT-qPCR and show significantly different expression 14 days after ligation via IHC. Our findings verify the expression of hub DEGs related to ferroptosis in IH and elucidate the potential relationship between ferroptosis and IH, providing more evidence about the vital role of ferroptosis in IH.

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“…Blocking SLC7A11 transporter activity leads to glutathione depletion and inactivation of phospholipid hydroperoxide glutathione peroxidase 4 (GPX4) and further induces ferroptosis [ 6 , 7 ]. In addition, mucin 1 (MUC1) is a ferroptosis-related gene that forms a complex with xCT and protects against treatment with erastin [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling

Liang

Wang

et al. 2022

Cell Death Discov.

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Endometriosis is a chronic disorder characterized by the implantation of endometrial glands and stroma outside the uterus. However, the pathogenesis of endometriosis is still unclear. To date, there is no fully effective treatment without trauma because of various side effects. Recent data suggest that ferroptosis is a novel recognized form of nonapoptosis-regulated cell death characterized by iron-dependent and lethal lipid peroxidation accumulation, showing great promise in the treatment of many diseases. In the present study, we verified that erastin induced ferroptosis in ectopic endometrial stromal cells (EESCs). Furthermore, we found that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was decreased during erastin-induced ferroptosis. Knockdown of MALAT1 significantly aggravated the inhibition of cell viability and increased intracellular iron, Liperfluo, and MDA levels in EESCs upon erastin treatment. Mechanistically, we demonstrated that MALAT1 served as a competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore, erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon erastin treatment via miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.

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Integrative analysis of ferroptosis-related genes in ulcerative colitis

Cited by 24 publications

References 26 publications

Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3β/Keap1-Nrf2-GPX4 Pathway

Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3β/Keap1-Nrf2-GPX4 Pathway

Expression profiles and functions of ferroptosis-related genes in intimal hyperplasia induced by carotid artery ligation in mice

Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling

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