Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (&lt;i&gt;NEAT1&lt;/i&gt;) Facilitates Foam Cell Formation and Atherosclerosis Progression Through the miR-17-5p/Itchy E3 Ubiquitin Protein Ligase (ITCH)/Liver Kinase B1 (LKB1) Axis

Huang, Haifen; Peng, Bin; Chen, Qingyong; Wang, Yi; Li, Ren

doi:10.1253/circj.cj-23-0769

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…Liraglutide (LRG), a glucagon-like peptide 1 analog (GLP1A), increases the phosphorylation of LKB1 by promoting the secretion of FGF21, thereby inhibiting TG synthesis in macrophages [ 61 ]. The E3 ubiquitin ligase Itchy E3 ubiquitin-protein ligase (ITCH) can promote LDL uptake and lipid accumulation in macrophages by mediating the ubiquitination and degradation of LKB1 [ 62 ].…”

Section: Lipid Metabolism In Tamsmentioning

confidence: 99%

The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma

Xie,

Zeng,

Zhang

et al. 2024

Cancer Immunol Immunother

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In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the oncogenic process. The microenvironment of hepatocellular carcinoma (HCC) is characterized by a pronounced infiltration of TAMs, underscoring their pivotal role in modulating the trajectory of the disease. Amidst the evolving therapeutic paradigms for HCC, the strategic reprogramming of metabolic pathways presents a promising avenue for intervention, garnering escalating interest within the scientific community. Previous investigations have predominantly focused on elucidating the mechanisms of metabolic reprogramming in cancer cells without paying sufficient attention to understanding how TAM metabolic reprogramming, particularly lipid metabolism, affects the progression of HCC. In this review article, we intend to elucidate how TAMs exert their regulatory effects via diverse pathways such as E2F1-E2F2-CPT2, LKB1-AMPK, and mTORC1-SREBP, and discuss correlations of TAMs with these processes and the characteristics of relevant pathways in HCC progression by consolidating various studies on TAM lipid uptake, storage, synthesis, and catabolism. It is our hope that our summary could delineate the impact of specific mechanisms underlying TAM lipid metabolic reprogramming on HCC progression and provide useful information for future research on HCC and the development of new treatment strategies.

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Section: Lipid Metabolism In Tamsmentioning

confidence: 99%

The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma

Xie,

Zeng,

Zhang

et al. 2024

Cancer Immunol Immunother

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The role of splicing events in the inflammatory response of atherosclerosis: molecular mechanisms and modulation

Wang,

Xuan

et al. 2024

Front. Immunol.

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Atherosclerosis is a chronic inflammatory disease characterized by persistent inflammatory responses throughout all stages of its progression. Modulating these inflammatory responses is a promising avenue for the development of cardiovascular disease therapies. Splicing events modulate gene expression and diversify protein functionality, exerting pivotal roles in the inflammatory mechanisms underlying atherosclerosis. These insights may provide novel opportunities for developing anti-inflammatory therapies for this disease. This article systematically discusses the diverse splice variants and how splicing events impact the inflammatory response in atherosclerosis via endothelial cells, macrophages, and vascular smooth muscle cells, highlighting their underlying molecular mechanisms and implications. Furthermore, this study summarizes clinical evidence supporting splicing-related molecules as diagnostic biomarkers and therapeutic targets in atherosclerosis. Lastly, we outline the current challenges and future research directions concerning splicing events and inflammatory responses in atherosclerosis. This offers a novel perspective and evidence for formulating new therapeutic strategies aimed at lowering the risk of atherosclerosis.

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Itchy E3 Ubiquitin Ligase-Mediated Ubiquitination of Ferritin Light Chain Contributes to Endothelial Ferroptosis in Atherosclerosis

Zeng,

Fu,

Xia

et al. 2024

IJMS

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This research seeks to investigate the function and fundamental mechanisms of Itchy E3 ubiquitin ligase (ITCH), a HECT (homologous to E6AP carboxyl terminus)-type E3 ubiquitin ligase, in endothelial ferroptosis, particularly in the context of atherosclerosis, which has been underexplored. The levels of ITCH protein in the aortas of mice with atherosclerosis were analyzed. Constructs for ITCH RNA interference were generated and introduced into human aortic endothelial cells (HAECs). The findings indicated that ITCH protein expression was elevated in atherosclerotic mice and HAECs exposed to oxidized low-density lipoprotein (ox-LDL). ITCH downregulation significantly mitigated ox-LDL-induced endothelial injury and dysfunction. Reducing ITCH expression inhibited ox-LDL-induced endothelial ferroptosis. This study also revealed that ITCH mediates ox-LDL-induced ubiquitin-dependent degradation of ferritin light chain (FTL) in HAECs. The protective impact of ITCH knockdown against ox-LDL-induced ferroptosis and endothelial injury was reversed by FTL siRNA. Additionally, in vivo experiments showed that inhibiting ITCH reduced atherosclerosis progression and reversed ferroptosis in the aorta, with an associated increase in FTL protein expression in the aortas of mice. This study demonstrates that ITCH interacts with and regulates the stability of the FTL protein via the ubiquitin–proteasome system, contributing to ox-LDL-induced ferroptosis and endothelial cell dysfunction. Targeting components of the ITCH-FTL pathway holds potential as a therapeutic strategy against atherosclerosis.

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Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (<i>NEAT1</i>) Facilitates Foam Cell Formation and Atherosclerosis Progression Through the miR-17-5p/Itchy E3 Ubiquitin Protein Ligase (ITCH)/Liver Kinase B1 (LKB1) Axis

Cited by 3 publications

References 37 publications

The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma

The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma

The role of splicing events in the inflammatory response of atherosclerosis: molecular mechanisms and modulation

Itchy E3 Ubiquitin Ligase-Mediated Ubiquitination of Ferritin Light Chain Contributes to Endothelial Ferroptosis in Atherosclerosis

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