The p-STAT3/ANXA2 axis promotes caspase-1-mediated hepatocyte pyroptosis in non-alcoholic steatohepatitis

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Nov. 2, 2022

Abstract Background To explore the roles of Annexin A2 (ANXA2) on hepatocyte pyroptosis and hepatic fibrosis in nonalcoholic steatohepatitis (NASH) underlying molecular mechanism. Methods Bioinformatics analyses were performed transcriptome data liver tissues from mice patients with for screening pyroptosis-related differential genes. The vivo NASH mouse model vitro cellular established. expression levels Anxa2/ ANXA2 quantified. Then, upstream transcription factor Anxa2 was screened by ChIP-Seq experimentally verified. effects p-STAT3/ANXA2 axis Caspase-1 mediated explored experiments. Results suggested that significantly up-regulated both scoring high pyroptotic activity. Experimental showed positively associated development fibrosis. As a ANXA2, p-STAT3 can bind to promoter promote its transcription. inhibition suppress fibrosis, which reversed after over-expression . verified as player By specifically inhibiting Caspase-1, promotion effect be weakened. Conclusion promoted at level, thus activating NASH.

Language: Английский

---

Burning down the house: Pyroptosis in the tumor microenvironment of hepatocellular carcinoma

Life Sciences, Journal Year: 2024, Volume and Issue: 347, P. 122627 - 122627

Published: April 16, 2024

Language: Английский

---

Oxaliplatin induces pyroptosis in hepatoma cells and enhances antitumor immunity against hepatocellular carcinoma

British Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

---

Machine learning analysis identified NNMT as a potential therapeutic target for hepatocellular carcinoma based on PCD-related genes

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 3, 2025

Language: Английский

---

An immune cell activation signature reflected hepatocellular carcinoma heterogeneity and predicted clinical outcomes

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 28, 2025

Background The prognosis of hepatocellular carcinoma (HCC) remains challenging, and immune activation plays a critical role in cancer treatment. Identifying reliable activation-related prognostic markers is for predicting HCC patient outcomes. Method A six-gene signature was developed. value assessed by correlating the survival. robustness validated three independent Gene Expression Omnibus (GEO) datasets. Associations with clinical, genomic, transcriptomic features were also evaluated. Additionally, single-cell sequencing data analyzed to explore cell–cell interaction heterogeneity reflected signature. biological candidate gene RORC investigated, including chemotherapy resistance detailed regulatory mechanism affecting progression. clinical potential its downstream evaluated immunohistochemical (IHC) microarray. Results stratified patients into high-risk low-risk groups, samples exhibiting significantly shorter overall survival (median: 23.8 months, 95% CI: 20.6–41.8) than 83.2 69.6–NA, p < 0.001). Validation GEO datasets confirmed associated pathological stage negatively correlated PD-L1 expression, outperforming indicators 3-year TP53 mutations, genomic stability, canonical cancer-related pathways. Single-cell indicated that revealed HCC. Candidate promotes proliferation migration regulating CDC6 expression as transcription factor. Furthermore, multiple drug resistance, especially docetaxel paclitaxel. IHC valuable predictive biomarkers prognosis. Conclusion provides insights status robust tool application.

Language: Английский

---

Increased expression of DNAJC7 promotes the progression of hepatocellular carcinoma by influencing the cell cycle and immune microenvironment

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(5)

Published: May 2, 2025

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide owing to lack effective and early diagnostic tools therapeutic approaches. DNAJC7, a member DnaJ heat shock family, crucial in protein folding stability; however, its specific functions mechanisms HCC remain unclear. This study aimed explore role DNAJC7 progression evaluate potential clinical significance as prognostic marker. Public databases (TCGA, ICGC, GEO, TIMER) were used assess expression, correlations with parameters, related signaling pathways. Proliferation, migration, invasion, cell cycle assays performed function HCC. Immune infiltration associations checkpoint proteins analyzed using TIMER, Gene Set Enrichment Analysis (GSEA) was enriched expression higher tissues than adjacent normal associated advanced malignancy poor prognosis, including lower overall survival, progression-free disease-free survival. knockdown resulted reduced malignant behavior cells, S-phase arrest. Increased immune presence immunological molecules, CTLA4 PD-1. GSEA highlighted activation key pathways, WNT regulation. regulates tumor proliferation, evasion by acting an oncogene It can serve biomarker treatment target for

Language: Английский

---

Establishment and Clinical Application of the Nomogram Related to Risk or Prognosis of Hepatocellular Carcinoma: A Review

Journal of Hepatocellular Carcinoma, Journal Year: 2023, Volume and Issue: Volume 10, P. 1389 - 1398

Published: Aug. 1, 2023

Abstract: Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy, accounting for approximately 90% of all cancers, with high mortality and a poor prognosis. A large number predictive models have been applied that integrate multiple clinical factors biomarkers to predict prognosis HCC. Nomograms, as easy-to-use prognostic models, are widely used probability outcomes. We searched PubMed keywords "hepatocellular carcinoma" "nomogram", 974 relative literatures were retrieved. According construction methodology real validity nomograms, in this study, 97 nomograms HCC selected 77 publications. These established based on more than 100,000 patients, covering seven main The research data 56 articles from hospital-based 13 provided external validation results nomogram. In addition AFP, tumor size, number, stage, vascular invasion, age, other common risk included HCC-related nomogram, biomarkers, including gene mRNA expression, polymorphisms, signature, etc. also nomograms. establishment, assessment these discussed depth. This study would help clinicians construct select appropriate guide precise judgment treatments. Keywords: hepatocellular carcinoma, prognosis, biomarker, precision medicine

Language: Английский

---

Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4783 - 4783

Published: April 27, 2024

Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon injury the ensuing sterile inflammation have also been attributed a role HCC pathogenesis. Cargoes extracellular vesicles (EVs) and/or EVs themselves listed among circulating DAMPs but only partially investigated HCC. Mitochondria-derived (MDVs), subpopulation EVs, are another missing link comprehension mechanisms underlying onset progression biology. involved growth, dissemination, angiogenesis, immunosurveillance escape. contribution MDVs these processes is presently unclear. Pyroptosis triggers systemic through caspase-dependent apoptotic cell death implicated tumor immunity. analysis this process, together with MDV characterization, may help capture relationship development, mitochondrial quality control, inflammation. combination immune checkpoint inhibitors (i.e., atezolizumab bevacizumab) has approved as synergistic first-line treatment for unresectable or advanced lack biomarkers that allow prediction response and, therefore, patient selection, major unmet need. Herein, we overview linking dysfunction, pyroptosis, discuss how immunotherapy targets, at least partly, routes.

Language: Английский

---

Identification and validation of immunity- and disulfidptosis-related genes signature for predicting prognosis in ovarian cancer

Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32273 - e32273

Published: June 1, 2024

Language: Английский

---

Mitochondrial Quality Control Processes at the Crossroads of Cell Death and Survival: Mechanisms and Signaling Pathways

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7305 - 7305

Published: July 3, 2024

Biological aging results from an accumulation of damage in the face reduced resilience. One major driver is cell senescence, a state which cells remain viable but lose their proliferative capacity, undergo metabolic alterations, and become resistant to apoptosis. This accompanied by complex cellular changes that enable development senescence-associated secretory phenotype (SASP). Mitochondria, organelles involved energy provision activities essential for regulating survival death, are negatively impacted aging. The age-associated decline mitochondrial function also chronic low-grade sterile inflammation. latter shares some features mediators with SASP. Indeed, unloading damage-associated molecular patterns (DAMPs) at extracellular level can trigger inflammatory responses mitochondria contribute generation DAMPs pro-inflammatory properties. extrusion DNA (mtDNA) via outer membrane permeabilization under apoptotic stress triggers senescence programs. Additional pathways For instance, pyroptosis caspase-dependent inducer systemic inflammation, elicited mtDNA release contributes Herein, we overview mechanisms may link dyshomeostasis, pyroptosis, discuss how these could be exploited as targets alleviating burden achieving healthy longevity.

Language: Английский

---