ACSL4 promotes ferroptosis and M1 macrophage polarization to regulate the tumorigenesis of nasopharyngeal carcinoma

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 122, P. 110629 - 110629

Published: July 13, 2023

Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor with high incidence recurrence rate. The crosstalk between ferroptosis tumor-associated macrophages (TAMs) thought to have major implications in interfering cancers. We intended explore the effect of acyl-CoA synthetase long-chain family member 4 (ACSL4) on pathogenesis NPC via TAMs.Differential genes patients were analyzed using publicly available databases, ferroptosis-related gene ACSL4 was identified. Expression cell lines xenografted mice examined. Colony formation, proliferation, migration, invasion assessed. abundance epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Vimentin) confirmed. Lipid peroxidation levels related measured. Clophosome administered determine role TAMs mice.Low observed CNE-2 5-8F cells. Erastin (a inducer) increased lipid peroxidation, decreased viability, colony migration invasion, inhibited EMT. Moreover, promoted M2 M1 macrophage polarization. effects erastin additive. Ferrostatin-1, an inhibitor ferroptosis, exerted opposite reversed beneficial overexpression. In xenograft mice, clophosome hindered growth NPC, extra slightly enhanced antitumor ACSL4.Our findings indicated that at least through macrophages, providing potential direction for therapy.

Language: Английский

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CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101015 - 101015

Published: Oct. 29, 2023

Therapeutic outcome of sorafenib in hepatocellular carcinoma (HCC) is undermined by the development drug resistance. This study aimed to identify critical microRNA (miRNA) which responsible for resistance at genomic level. CRISPR/Cas9 screen followed gain- and loss-of-function assays both vitro vivo were applied role miR-3689a-3p mediating response HCC. The upstream downstream molecules their mechanism action investigated. screening identified was most up-regulated miRNA sensitive Knockdown significantly increased resistance, while its overexpression sensitized HCC treatment. Proteomic analysis revealed that effect related copper-dependent mitochondrial superoxide dismutase type 1 (SOD1) activity. Mechanistically, targeted 3′UTR intracellular copper chaperone (CCS) suppressed expression. As a result, disrupted trafficking reduced SOD1-mediated scavenge oxidative stress eventually caused cell death CCS blunted Clinically, down-regulated predicted favorable prognosis patients. Our findings provide comprehensive evidence as positive regulator potential druggable target improving treatment

Language: Английский

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Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1166 - 1166

Published: April 13, 2023

The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways critical for cell survival or death. balance between autophagy regulates liver turnover maintains intracellular homeostasis. However, the often dysregulated in many cancers, including HCC. may be either independent parallel one influence other. inhibit promote apoptosis, thus regulating fate cancer cells. In this review, concise overview HCC presented, with emphasis on new developments, role endoplasmic reticulum stress, implication microRNAs gut microbiota. characteristics associated specific disease also described brief description provided. initiation, progress metastatic potential reviewed experimental evidence indicating an interplay extensively analyzed. ferroptosis, recently pathway regulated death, presented. Finally, therapeutic implications drug resistance examined.

Language: Английский

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The ACSL4 Network Regulates Cell Death and Autophagy in Diseases

Biology, Journal Year: 2023, Volume and Issue: 12(6), P. 864 - 864

Published: June 15, 2023

Lipid metabolism, cell death, and autophagy are interconnected processes in cells. Dysregulation of lipid metabolism can lead to such as via ferroptosis apoptosis, while lipids also play a crucial role the regulation autophagosome formation. An increased autophagic response not only promotes survival but causes death depending on context, especially when selectively degrading antioxidant proteins or organelles that promote ferroptosis. ACSL4 is an enzyme catalyzes formation long-chain acyl-CoA molecules, which important intermediates biosynthesis various types lipids. found many tissues particularly abundant brain, liver, adipose tissue. linked variety diseases, including cancer, neurodegenerative disorders, cardiovascular disease, acute kidney injury, metabolic disorders (such obesity non-alcoholic fatty liver disease). In this review, we introduce structure, function, ACSL4; discuss its ferroptosis, autophagy; summarize pathological function; explore potential implications targeting treatment diseases.

Language: Английский

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Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 67(1), P. 19 - 40

Published: Sept. 15, 2023

Language: Английский

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