SLC6A14 facilitates epithelial cell ferroptosis via the C/EBPβ-PAK6 axis in ulcerative colitis

Chen, Yanjun; Yan, Wenying; Chen, Yuqi; Zhu, Jinghan; Wang, Jiayu; Huang, Jin; Wu, Hongya; Zhang, Guangbo; Zhan, Shenghua; Xi, Qinhua; Shi, Tongguo; Chen, Weichang

doi:10.1007/s00018-022-04594-7

Cited by 12 publications

(6 citation statements)

References 38 publications

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“…Further analysis has revealed that SLc6A14 inhibits the expression of p21 (RAc1)-activated kinase 6 (PAK6) and the knockdown of PAK6 abolishes the effects of SLc6A14 on RSL3-induced ferroptosis in caco-2 cells. Mechanistically, SLc6A14 promotes ferroptosis in Uc by enhancing the expression of ccAAT enhancer binding protein β (c/EBPβ) and its binding activity to inhibit PAK6 (83), providing the SLc6A14-c/EBPβ-PAK6 axis-mediated ferroptosis a potential therapeutic target for colitis.…”

Section: Targeting Ferroptosis For the Treatment Of Ibdmentioning

confidence: 99%

Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review)

et al. 2023

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Ferroptosis, a novel form of regulated cell death, is characterized by the accumulation of labile iron and lipid peroxidation, and the excessive production of reactive oxygen species (ROS). Although ferroptosis lies at the center of crucial biological activities involving O 2 , iron and polyunsaturated fatty acids (PUFAs), which are essential for cell proliferation and growth, the interaction between these molecules could also mediate the accumulation of toxic levels of ROS and lipid peroxides, which can then cause damage to cellular membranes and ultimately result in cell death. Recent reports have indicated that ferroptosis participates in the development and progression of inflammatory bowel disease (IBD), offering a new exploratory field which may aid in the more in-depth understanding of the pathogenesis and therapeutic targets of IBd. Of note, the mitigation of the characteristic features of ferroptosis, such as depleted glutathione (GSH) levels, inactivated glutathione peroxidase 4 (GPX4), elevated levels of lipid peroxidation and iron overload significantly relieve IBD. This has attracted the attention of researches aiming to examine therapeutic agents that inhibit ferroptosis in IBd, including radical-trapping antioxidants, enzyme inhibitors, iron chelators, protein degradation inhibitors, stem cell-derived exosomes and oral N-acetylcysteine or glutathione. The present review summarizes and discusses the current data that implicate ferroptosis in the pathogenesis of IBd and its inhibition as a novel alternate therapeutic target for IBd. The mechanisms and key mediators of ferroptosis, including GSH/GPX4, PUFAs, iron and organic peroxides are also discussed. Although the field is relatively new, the therapeutic regulation of ferroptosis has exhibited promising outcomes as a novel treatment avenue for IBd. Contents 1. Introduction 2. The mechanisms of ferroptosis 3. Key mediators of ferroptosis 4. Role of ferroptosis in the pathogenesis of IBd 5. Role of ferroptosis in the pathogenesis of other intestinal diseases 6. Targeting ferroptosis for the treatment of IBd 7. Targeting ferroptosis in other intestinal diseases 8. conclusions and future perspectives

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Section: Targeting Ferroptosis For the Treatment Of Ibdmentioning

confidence: 99%

Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review)

et al. 2023

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“…Speci cally, SLC6A14 augments the occurrence of ferroptosis in UC by repressing P21 (RAC1)-activated kinase 6 (PAK6) expression through CCAAT enhancer binding protein beta (C/EBPβ). [12] Additionally, acyl-CoA synthetase family member 2 (ACSF2) may serve as a promising target for ferroptosis in patients with IBD. [13] Meanwhile, several antioxidants and anti-in ammatory substances have been reported to in uence the outcome of experimental colitis by regulating intricate process of ferroptosis.…”

Section: Potential Association Of Ferroptosis With Ibdmentioning

confidence: 99%

“…Specifically, SLC6A14 augments the occurrence of ferroptosis in UC by repressing P21 (RAC1)-activated kinase 6 (PAK6) expression through CCAAT enhancer binding protein beta (C/EBPβ). [12]…”

mentioning

confidence: 99%

Ferroptosis: A therapeutic opportunity of inflammatory bowel disease

Ye,

Liu,

Jing

et al. 2024

Chinese Medical Journal

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“…ChIP was performed as described previously [19]. Brie y, cells were crosslinked with 1% formaldehyde and then cleaved with a cracking solution.…”

Section: Chromatin Immunoprecipitation (Chip)mentioning

confidence: 99%

HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification

Wang,

Zhu,

Jinhan

et al. 2023

Preprint

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HES1 plays a critical role in promoting tumor progression, but the underlying mechanisms are only partially understood. Here, we found that HES1 expression was significantly higher in CRC tissues than that in adjacent normal tissues. Moreover, high HES1 expression is associated with poor survival in CRC patients. HES1 knockdown markedly inhibited cell growth and metastasis both in vitro and in vivo. Additionally, silencing of HES1 suppressed aerobic glycolysis of CRC cells. Mechanistic studies revealed that HES1 knockdown decreased the expression of GLUT1, a key gene of aerobic glycolysis, in CRC cells. GLUT1 overexpression abolished the effects of HES1 knockdown on cell aerobic glycolysis, proliferation, migration and invasion. ChIP-PCR and dual-luciferase reporter gene assay showed that HES1 directly bound the promoter of IGF2BP2 and promoted IGF2BP2 expression. Furthermore, our data indicated that IGF2BP2 recognized and bound the m6A site in the GLUT1 mRNA and enhanced its stability. Taken together, our findings suggest that HES1 has a significant promotion effect on CRC aerobic glycolysis and progression by enhancing the stability of m6A-modified GLUT1 mRNA in an IGF2BP2-dependent manner.

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SLC6A14 facilitates epithelial cell ferroptosis via the C/EBPβ-PAK6 axis in ulcerative colitis

Cited by 12 publications

References 38 publications

Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review)

Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review)

Ferroptosis: A therapeutic opportunity of inflammatory bowel disease

HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification

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