AGE-RAGE synergy influences programmed cell death signaling to promote cancer

Waghela, Bhargav N.; Vaidya, Foram U.; Ranjan, Kishu; Chhipa, Abu Sufiyan; Tiwari, Budhi Sagar; Pathak, Chandramani

doi:10.1007/s11010-020-03928-y

Cited by 67 publications

(48 citation statements)

References 148 publications

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“…Deimination in estrogen signaling may be of considerable interest as estrogen receptors are expressed broadly in innate and adaptive immune-related cells and also affect cytokine production, and are furthermore involved in immune regulation in the tumour environment [66]. The AGE-RAGE signaling pathway, also enriched in deiminated proteins in EVs, relates to diabetic complications [67], age-and stress-related arterial diseases [68] as well as playing multifaceted roles in cancer progression, including cell death control (apoptosis, autophagy and necroptosis), cytokine release and EMT, including in chronic mucosal inflammation [69][70][71]. Deimination enrichment in the relaxin signaling pathway was also identified to be specific to plasma EVs.…”

Section: Discussionmentioning

confidence: 99%

Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

D’Alessio

Thorgeirsdottir

Kraev

et al. 2021

Biology

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The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis.

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Section: Discussionmentioning

confidence: 99%

Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

D’Alessio

Thorgeirsdottir

Kraev

et al. 2021

Biology

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“…In the AGE-RAGE signaling pathway, AGEs interact through AGE-RAGE to bind and trigger RAGEs that play a key role in inflammation and oxidative stress [ 45 ]. Furthermore, AGE-RAGE acts synergistically to affect programmed cell death signaling and promote cancer development [ 46 ]. In the IL-17 signaling pathway, IL-17 is a pleiotropic proinflammatory cytokine involved in various processes such as host defense, inflammatory diseases, tissue repair, and cancer development [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Revealing the Mechanism of Astragali Radix against Cancer-Related Fatigue by Network Pharmacology and Molecular Docking

Xie

Zhou

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Cancer-related fatigue (CRF) is an increasingly appreciated complication in cancer patients, which severely impairs their quality of life for a long time. Astragali Radix (AR) is a safe and effective treatment to improve CRF, but the related mechanistic studies are still limited. Objective. To systematically analyze the mechanism of AR against CRF by network pharmacology. Methods. TCMSP was searched to obtain the active compounds and targets of AR. The active compound-target (AC-T) network was established and exhibited by related visualization software. The GeneCards database was searched to acquire CRF targets, and the intersection targets with AR targets were used to make the Venny diagram. The protein-protein interaction (PPI) network of intersection targets was established, and further, the therapeutic core targets were selected by topological parameters. The selected core targets were uploaded to Metascape for GO and KEGG analysis. Finally, AutoDock Vina and PyMOL were employed for molecular docking validation. Results. 16 active compounds of AR were obtained, such as quercetin, kaempferol, 7-O-methylisomucronulatol, formononetin, and isorhamnetin. 57 core targets were screened, such as AKT1, TP53, VEGFA, IL-6, and CASP3. KEGG analysis manifested that the core targets acted on various pathways, including 137 pathways such as TNF, IL-17, and the AGE-RAGE signaling pathway. Molecular docking demonstrated that active compounds docked well with the core targets. Conclusion. The mechanism of AR in treating CRF involves multiple targets and multiple pathways. The present study laid a theoretical foundation for the subsequent research and clinical application of AR and its extracts against CRF.

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“…Once activated, Akt controls a number of downstream cellular processes, including apoptosis, protein synthesis, metabolism, and cell cycle, by phosphorylating a range of substrates (Martini et al 2014). The AGE-RAGE signaling pathway influences NAPDH and enhances oxidative stress, which activates the NF-κB signaling pathway and further stimulates the production of cytokines and growth factors, thereby damaging cells and tissues (Waghela et al 2021). These findings are consistent with the findings of GO enrichment.…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of the potential effect of therapeutic miRNA-mRNA pairs on ferroptosis in small cell lung cancer by bioinformatics analysis

2021

Preprint

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Owing to the high mortality rate of small cell lung cancer (SCLC), it is essential to determine a novel therapeutic approach for treating patients with SCLC. miRNA is a type of non-coding RNA that plays a role in translational control. By applying this identity, it is applicable for treating patients using miRNA and nanotechnology. Ferroptosis is a newly discovered type of programmed cell death. Accumulated evidence suggests the possibility of using ferroptosis in treating patients with SCLC. Thus, identifying potential therapeutic miRNA-mRNA pairs that have an impact on ferroptosis will be valuable. In the in silico analysis, several Gene Expression Omnibus datasets were analyzed. The results were verified using other data. Here, we report that the miR-30 family and KIF11 pair have a crucial influence on SCLC cells, which may also affect ferroptosis.

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AGE-RAGE synergy influences programmed cell death signaling to promote cancer

Cited by 67 publications

References 148 publications

Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

Revealing the Mechanism of Astragali Radix against Cancer-Related Fatigue by Network Pharmacology and Molecular Docking

Identification and verification of the potential effect of therapeutic miRNA-mRNA pairs on ferroptosis in small cell lung cancer by bioinformatics analysis

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