Inflammation and tumor progression: signaling pathways and targeted intervention

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 12, 2021

Abstract Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates progression treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation dendritic cells (DCs) antigen presentation, leading anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers activators transcription (JAK-STAT), toll-like receptor (TLR) cGAS/STING, mitogen-activated protein kinase (MAPK); factors, including cytokines (e.g., interleukin (IL), interferon (IFN), necrosis (TNF)-α), chemokines C-C motif chemokine ligands (CCLs) C-X-C (CXCLs)), growth factors vascular endothelial (VEGF), transforming (TGF)-β), inflammasome; well metabolites prostaglandins, leukotrienes, thromboxane, specialized proresolving mediators (SPM), have been identified pivotal regulators initiation resolution inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, SPM developed specifically modulate in cancer therapy, with some these already undergoing clinical trials. Herein, we discuss crosstalk between processes. We also highlight potential targets for harnessing cancer.

Language: Английский

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HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 23, 2021

Abstract N6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one the ways which cancer cells survive hypoxia. However, possible involvement m6A modification mRNA hypoxia-induced autophagy was unexplored hepatocellular carcinoma (HCC). In this study, specific variations YTHDF1 expression were detected YTHDF1-overexpressing, -knockout, -knockdown HCC cells, organoids, patient-derived xenograft (PDX) murine models. significantly correlated vitro; significant overexpression tissues associated with poor prognosis. Multivariate cox regression analysis identified as an independent prognostic factor patients HCC. Multiple models confirmed that deficiency inhibited autophagy, growth, metastasis. Luciferase reporter assays chromatin immunoprecipitation demonstrated HIF-1α regulated transcription directly binding to promoter region under The results methylated sequencing, proteomics, polysome profiling indicated contributed translation autophagy-related genes ATG2A ATG14 m6A-modified mRNA, thus facilitating malignancy Taken together, HIF-1α-induced progression via promoting m6A-dependent manner. Our findings suggest potential biomarker therapeutic target for

Language: Английский

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Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity

ACS Nano, Journal Year: 2022, Volume and Issue: 16(6), P. 9228 - 9239

Published: May 27, 2022

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from resources, especially daily food, implies a promising direction for exploring treatment strategies human diseases. Here, we report biocompatible nanozyme prepared chlorogenic acid (ChA), major bioactive product coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation GPX4-catalyzed lipid repair systems. In vivo, dramatically suppressed the tumor growth in HepG2-tumor-bearing mice negligible side toxicity. Particularly, hepatoma H22-bearing mice, recruited massive tumor-infiltrating immune cells including T cells, NK macrophages, thereby converting "cold" "hot" tumors activating systemic antitumor responses. Taken together, our study suggests product-derived coffee can serve biologically safe anticancer therapeutics may aid development nanotechnology-based immunotherapeutic.

Language: Английский

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Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma

Cancers, Journal Year: 2020, Volume and Issue: 12(9), P. 2622 - 2622

Published: Sept. 14, 2020

The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes HCC, including cancer cell growth, epithelial mesenchymal transition (EMT), metastasis, chemoresistance. In this review, we summarize recent discoveries, which specific (lncRNA/circRNA-miRNA-mRNA) HCC discuss their clinical significance.

Language: Английский

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Epigenetic regulation of ferroptosis via ETS1/miR-23a-3p/ACSL4 axis mediates sorafenib resistance in human hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Jan. 3, 2022

Abstract Background Drug resistance to sorafenib greatly limited the benefits of treatment in patients with hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate development drug resistance. The key miRNA regulators related clinical outcome and their molecular mechanisms remain be identified. Methods significance miRNA-related epigenetic changes sorafenib-resistant HCC was evaluated by analyzing publicly available databases in-house human tissues. biological functions miR-23a-3p were investigated both vitro vivo. Proteomics bioinformatics analyses conducted identify that regulating miR-23a-3p. Luciferase reporter assay chromatin immunoprecipitation (ChIP) used validate binding relationship its targets. Results We found most prominent HCC, which overexpressed non-responders indicated poor survival relapse. Sorafenib-resistant cells exhibited increased transcription an ETS Proto-Oncogene 1 (ETS1)-dependent manner. CRISPR-Cas9 knockout improved response as well orthotopic tumours. analysis suggested sorafenib-induced ferroptosis pathway suppressed reduced cellular iron accumulation lipid peroxidation. MiR-23a-3p directly targeted 3′-untranslated regions (UTR) ACSL4, positive regulator ferroptosis. inhibitor rescued ACSL4 expression induced ferrotoptic cell death sorafenib-treated cells. co-delivery siRNA abolished response. Conclusion Our study demonstrates ETS1/miR-23a-3p/ACSL4 axis contributes through findings suggest could a potential target improve responsiveness patients.

Language: Английский

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Knowledge Mapping of Immunotherapy for Hepatocellular Carcinoma: A Bibliometric Study

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 31, 2022

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and many patients are diagnosed with advanced disease. The treatment liver cancer has made significant strides in recent years, owing to practice immunotherapy drugs. Numerous studies have been published on for HCC; however, no relevant bibliometric study published. This aims gain a better understanding current situation identify potential new research directions by conducting analysis HCC.We searched Web Science Core Collection (WoSCC) articles related HCC. Three software (VOSviewer, CiteSpace, python) were primarily used assess contribution co-occurrence relationships various countries/regions, institutes, journals, and, authors as well hotspots promising future trends this field.A total 1,641 English between 2011 2020 collected, number increasing nearly every year. majority publications originated from China (n = 893, 54.42%), followed United States Japan. Sun Yat-sen University contributed 97, 5.91%). Nakatsura Tetsuya 26) Llovet JM 366) ranked first top ten co-cited authors. Cancer Immunology Immunotherapy was productive academic journal HCC [n 46, 2.80%; impact factor (IF) 6.9679]. Aggregation identification critical nodes network demonstrated shift field immunotherapy. Initially, predominantly "glypican-3", "cytokine-induced killer cells", "ny-eso-1", while emphasis shifted years "landscape", "camrelizumab", "combination therapy", "immune score".Increased attention paid advancement At moment, active frontiers focused immunological landscape cancer, screening population that can benefit immunotherapy, clinical application immune checkpoint inhibitors, particularly combination other therapeutic options (such local therapy targeted therapy).

Language: Английский

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Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Aug. 30, 2021

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignancies globally. Despite aggressive and multimodal treatment regimens, overall survival HCC patients remains poor. Main Circular RNAs (circRNAs) are noncoding (ncRNAs) with covalently closed structures tissue- or organ-specific expression patterns in eukaryotes. They highly stable have important biological functions, including acting as microRNA sponges, protein scaffolds, transcription regulators, translation templates interacting RNA-binding protein. Recent advances indicated that circRNAs present abnormal tissues their dysregulation contributes to initiation progression. Furthermore, researchers revealed some might serve diagnostic biomarkers drug targets clinical settings. In this review, we systematically evaluate characteristics, biogenesis, mechanisms functions further discuss current shortcomings potential directions prospective studies on liver cancer-related circRNAs. Conclusion CircRNAs a novel class ncRNAs play significant role progression, but internal applications need investigation.

Language: Английский

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Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Jan. 6, 2023

Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal drug by targeting ferroptosis. The present study aimed explore the association fatty acid synthase (FASN) sorafenib via regulation ferroptosis provide novel strategy overcome HCC patients.Intracellular levels lipid peroxides, glutathione, malondialdehyde, Fe2+ were measured as indicators status. Biological information analyses, immunofluorescence assays, western blot co-immunoprecipitation analyses conducted elucidate functions FASN in HCC. Both vitro vivo examine antitumor effects combination orlistat CalcuSyn software was used calculate index.Solute carrier family 7 member 11 (SLC7A11) found play an important role mediating resistance. up-regulation antagonize SLC7A11-mediated thereby promoted Mechanistically, enhanced sorafenib-induced binding hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination proteasomal degradation HIF1α, subsequently enhancing transcription SLC7A11. Orlistat, inhibitor FASN, had significant synergistic reversed both vivo.Targeting FASN/HIF1α/SLC7A11 pathway resensitized cells sorafenib. superior sorafenib-resistant cells.

Language: Английский

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Polyphyllin I induced ferroptosis to suppress the progression of hepatocellular carcinoma through activation of the mitochondrial dysfunction via Nrf2/HO-1/GPX4 axis

Phytomedicine, Journal Year: 2023, Volume and Issue: 122, P. 155135 - 155135

Published: Oct. 12, 2023

Language: Английский

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Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

Cancer Biology and Medicine, Journal Year: 2023, Volume and Issue: 20(1), P. 25 - 43

Published: Jan. 12, 2023

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, process formation new blood vessels, required for cancer cells to obtain nutrients and oxygen. HCC a typical hypervascular solid tumor with an aberrant vascular network angiogenesis that contribute its growth, progression, invasion, metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, endothelial growth factor receptor (VEGFR), platelet-derived (PDGFR), are considered effective strategies HCC, particularly advanced HCC. However, because survival benefits conferred by these modest, targets must be identified. Several recent studies have determined underlying molecular mechanisms, including pro-angiogenic factors secreted cells, microenvironment, stem cells. In this review, we summarize roles factors; involvement hepatic stellate tumor-associated macrophages, neutrophils present in microenvironment; regulatory influence on Furthermore, discuss some clinically approved potential novel therapeutic A better understanding mechanisms may lead development more optimized treatment modalities

Language: Английский

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