Involvement of CircRNAs in regulating The “New Generation of Cancer Hallmarks”: A Special Depiction on Hepatocellular Carcinoma

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 196, P. 104312 - 104312

Published: Feb. 28, 2024

Language: Английский

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Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Metabolites, Journal Year: 2024, Volume and Issue: 14(6), P. 325 - 325

Published: June 8, 2024

Epigenetic and metabolic reprogramming alterations are two important features of tumors, their reversible, spatial, temporal regulation is a distinctive hallmark carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, new entry point for tumor therapy. Moreover, drives hepatocellular carcinoma (HCC) initiation progression, highlighting significance metabolism in this disease. Exploring inter-regulatory relationship between epigenetic modification has become one hot directions current research. As viral etiologies have given way to dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it urgent that complex molecular pathways linking them hepatocarcinogenesis be explored. However, how aberrant crosstalk modifications affects MASLD-induced HCC lacks comprehensive understanding. A better understanding linkages necessary improve treatment strategies. For reason, review examines interwoven landscape carcinogenesis context focusing regulating development interactions while also updating advances modification-based therapeutic drugs HCC.

Language: Английский

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m6A-mediated lnc-OXAR promotes oxaliplatin resistance by enhancing Ku70 stability in non-alcoholic steatohepatitis-related hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: July 25, 2024

The escalating prevalence of metabolic diseases has led to a rapid increase in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (NASH-HCC). While oxaliplatin (OXA)-based hepatic arterial infusion chemotherapy (HAIC) shown promise advanced-stage HCC patients, its efficacy NASH-HCC remains uncertain. This study aims assess the effectiveness OXA-based HAIC and elucidate mechanisms underlying OXA resistance NASH-HCC. key lncRNAs were screened through RNA-seq analysis NASH/non-NASH OXA-sensitive/OXA-resistant (OXA-S/R) tissues. biological functions lnc-OXAR (OXA resistance-related lncRNA NASH-HCC) verified series vitro vivo experiments. molecular mechanism was elucidated by fluorescence situ hybridization, immunoprecipitation-mass spectrometry (FISH), Immunoprecipitation-Mass Spectrometry (IP-MS), RNA pulldown, immunoprecipitation (RIP), methylated sequencing (MeRIP-Seq) dual-luciferase reporter assay. exhibited reduced responsiveness compared non-NASH HCC. We identified validated novel transcript namedlnc-OXAR, which played crucial role conferring Inhibition suppressed cell growth restored sensitivity both mouse models vitro. Mechanistically, recruited Ku70 cystatin A (CSTA), preventing degradation facilitating DNA double-strand break (DSB) repair, thereby promoting Additionally, WTAP-mediated m6A modification enhanced stability an IGF2BP2-dependent manner. Notably, silencing significantly response patient-derived xenograft (PDX) derived from treatment can be attributed upregulation lnc-OXAR. Our findings provide rationale for stratifying patients undergoing based on etiology. Lnc-OXAR holds as target overcoming improving prognosis.

Language: Английский

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Investigating the Anticancer and Antioxidant Potentials of a Polymer-Grafted Sodium Alginate Composite Embedded with CuO and TiO2 Nanoparticles

Journal of Polymers and the Environment, Journal Year: 2024, Volume and Issue: 32(6), P. 2713 - 2728

Published: March 25, 2024

Abstract In this study, we conducted the synthesis of a composite material by grafting an acrylonitrile-co-styrene (AN-co-St) polymer into sodium alginate and incorporating CuO (copper oxide) TiO 2 (titanium dioxide) nanoparticles. The primary objective was to investigate potential anticancer antioxidant activities material. First, nanoparticles were synthesized characterized for their size, morphology, surface properties. Subsequently, these integrated matrix, which had been grafted with AN-co-St polymer, resulting in formation To confirm successful nanoparticle incorporation assess structural integrity composite, various techniques such as X-ray diffraction analysis (XRD), scanning electron microscopy-energy dispersive (SEM-EDX), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA) employed. material’s then evaluated. vitro cell viability assays using HepG-2 line performed cytotoxic effects, while (DPPH) determine composite’s ability scavenge free radicals protect against oxidative stress. Preliminary results indicate that demonstrated promising activities. presence within contributed are known possess Furthermore, enhanced overall performance stability

Language: Английский

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BRD1 deficiency affects SREBF1-related lipid metabolism through regulating H3K9ac/H3K9me3 transition to inhibit HCC progression

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 17, 2025

Abstract BRD1 encodes a protein containing bromodomain, which is an essential component of histone acetyltransferase (HAT) complexes. These complexes play crucial role in the regulation gene transcription and modification chromatin structures. The aberrant expression frequently observed across range cancer types, including hepatocellular carcinomas (HCC). However, precise mechanisms through contributes to tumorigenesis, especially HCC, remain unclear. In our investigation, we have uncovered novel for as oncogene implicated lipid metabolism HCC progression. Specifically, deficiency impedes proliferation metastasis cells reducing accumulation droplets cholesterol levels. This effect mediated SREBF1-induced downregulation SCD1 cells. Mechanistically, ablation disrupts acetylation level H3K9, culminating subsequent trimethylation H3K9 (H3K9me3). Notably, H3K14ac partially colocalizes with H3K9me3 its methyltransferase SETDB1 from double labeling both at SREBF1 promoter. creation repressive environment, ultimately leading HCC. Furthermore, combinatorial use inhibitor simvastatin augments antitumor efficacy vivo. Collectively, findings underscore critical regulator SREBF1-associated participant progression distinct epigenetic regulatory mechanism. discoveries further suggest promising therapeutic approach treatment

Language: Английский

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Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 18, 2024

Abstract Background Nonalcoholic steatohepatitis (NASH) is a progressive manifestation of nonalcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the growing knowledge NASH HCC, association between two conditions remains be fully explored. Bioinformatics has emerged as valuable approach for identifying disease-specific feature genes, enabling advancements in prediction, prevention, personalized treatment strategies. Materials methods In this study, we utilized CellChat, copy number karyotyping aneuploid tumors (CopyKAT), consensus Non-negative Matrix factorization (cNMF), Gene set enrichment analysis (GSEA), variation (GSVA), Monocle, spatial co-localization, single sample gene (ssGSEA), Slingshot, Scissor algorithm analyze cellular immune landscape HCC. Through algorithm, identified three cell types correlating with phenotypic features subsequently developed novel clinical prediction model using univariate, LASSO, multifactor Cox regression. Results Our results revealed macrophages are significant pathological factor development HCC macrophage migration inhibitory (MIF) signaling pathway plays crucial role crosstalk at molecular level. We deduced prognostic genes (YBX1, MED8, KPNA2), demonstrating strong diagnostic capability both Conclusion These findings shed light on mechanisms shared providing insights

Language: Английский

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Liver Biopsy Handling of Metabolic-Associated Fatty Liver Disease (MAFLD): the Children’s Hospital of Eastern Ontario grossing protocol

Therapeutic Advances in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Metabolic-(non-alcoholic) associated fatty liver disease (MAFLD/NAFLD) has increasingly become a worldwide epidemic. It been suggested that renaming NAFLD to MAFLD is critical in identifying patients with advanced fibrosis and poor cardiovascular outcomes. There are concerns the progression non-alcoholic steatohepatitis (NASH) may constant drive future healthcare of children adolescents. necessity tackle emerging risk factors for NASH-associated hepatocellular carcinoma (HCC). In this narrative review, we present current protocol biopsy separated between pre-analytical, analytical, post-analytical handling. Genetic association investigations have identified single nucleotide polymorphisms implicated MAFLD-HCC, many which seem belong lipid metabolism pathways. PNPLA3 rs738409 variant, TM6SF2 rs58542926 MBOAT7 rs641738 GCKR variants be significantly susceptibility. disclosing comprehensive performed at Children’s Hospital Eastern Ontario, Ottawa, ON, Canada, support most recent Kulkarni-Sarin’s pledge rename MAFLD. Grossing key histologic, immunophenotypical, ultrastructure data properly preserving tissue molecular genomics data.

Language: Английский

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Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review

World Journal of Hepatology, Journal Year: 2024, Volume and Issue: 16(4), P. 537 - 549

Published: April 24, 2024

The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays critical role in progression metastasis. Lymphatic blood vessels are major routes for solid metastasis essential parts drainage conduits. However, recent studies have shown lymphatic endothelial cells (LECs) (BECs) also play multifaceted roles the beyond their structural functions, particularly hepatocellular carcinoma (HCC). This comprehensive review summarizes diverse played by LECs BECs HCC, including involvement angiogenesis, immune modulation, lymphangiogenesis, By providing detailed account interplay between LECs, BECs, this aims to shed light on future research directions regarding regulatory function potential therapeutic targets HCC.

Language: Английский

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The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 8061 - 8083

Published: Nov. 1, 2024

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder with rising prevalence. It begins lipid accumulation in hepatocytes and gradually progresses to Metabolic-associated steatohepatitis (MASH), fibrosis, cirrhosis, potentially hepatocellular carcinoma (HCC). The pathophysiology of MASLD complex involves multiple factors, oxidative stress playing crucial role. Oxidative drives the progression by causing cellular damage, inflammatory responses, making it key pathogenic mechanism. Nuclear Factor Erythroid 2-Related 2 / Heme Oxygenase-1 (Nrf2/HO-1) signaling axis provides robust multi-organ protection against spectrum endogenous exogenous insults, particularly stress. plays pivotal role mediating antioxidant, anti-inflammatory, anti-apoptotic responses. Many studies indicate that activating Nrf2/HO-1 pathway can significantly mitigate MASLD. This article examines highlights natural compounds protect targeting activation. findings holds great promise as therapeutic target for Keywords: NRF-2/HO-1 pathway, antioxidants, compounds, non-alcoholic fatty

Language: Английский

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Inflammation Beats Cholesterol: A Comment on the Unequivocal Driver of Cardiovascular Disease Risk

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(7), P. 2519 - 2519

Published: March 27, 2023

Despite advancements in the current standard of care, cardiovascular diseases continue to hold top spot as leading cause mortality worldwide. The development atherosclerosis is most common culprit behind ailments such myocardial infarction, stroke, and peripheral vascular disease. Consequently, it imposes a significant burden on life expectancy, quality life, morbidity, societal costs. Both increased cholesterol levels activation inflammatory cascade are known risk facts. Their relative weight spotlight curent biomedical research. Newly published data shed light role inflammation determining irrespective cholesterol-lowering therapies.

Language: Английский

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