Pyroptosis in inflammatory diseases and cancer

Rao, Zhiping; Zhu, Yu; Yang, Peng; Chen, Zhuang; Xia, Yuqiong; Qiao, Chaoqiang; Liu, Weijing; Deng, Hongzhang; Li, Jianxiong; Ning, Pengbo; Wang, Zhongliang

doi:10.7150/thno.71086

Cited by 173 publications

(103 citation statements)

References 125 publications

(145 reference statements)

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“…e mechanism of cell death varies. Apoptosis [18], pyroptosis [19], necrosis [20], and ferroptosis [21][22][23] are the most commonly observed. Recently, Tsvetkov et al found a copper-based mechanism that was completely different from the known mechanisms of cell death, and they named it "cuproptosis" [7].…”

Section: Discussionmentioning

confidence: 99%

A Noval Established Cuproptosis-Associated LncRNA Signature for Prognosis Prediction in Primary Hepatic Carcinoma

Luo

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The copper ion content in the body maintains homeostasis, and when dysregulated, it can produce cytotoxicity and induce cell death through a variety of pathways. Cuproptosis refers to copper ions combining directly with acylated molecules, leading to the accumulation of oligomerization of lipoylated protein and subsequent downregulation of iron-sulfur cluster proteins; this induces proteotoxic stress and cell death. This study on the relationship between cuproptosis-related lncRNAs (CRLns) and the prognosis of primary hepatic carcinoma (PHC) has important clinical guiding significance for the diagnosis and treatment of PHC. Prognosis-related CRLRs were identified via rank-sum tests, correlational analyses, and univariate Cox regression, and a CRLR risk-scoring model (CRLRSM) was constructed using LASSO Cox regression. Patients were divided into high-risk and low-risk groups based on the median CRLRSM scores. Variance analysis for cuproptosis-related genes, gene set enrichment analysis, and correlational analysis for risk and immunity were performed using boxplots. Quantitative polymerase chain reactions were used to verify the CRLR levels in PHC cell lines. The study results showed that patients in the CRLRSM high-risk group had worse survival rates than those in the low-risk group. The PHC stage and risk score were independent prognostic factors for hepatocellular carcinoma. There were 7 CRLRs (MIR210HG, AC099850.3, AL031985.3, AC012073.1, MKLN1-AS, KDM4A-AS1, and PLBD1-AS1) associated with PHC prognosis, primarily through cellular metabolism, growth, proliferation, apoptosis, and immunity. In conclusion, the overexpression of 7 CRLRs in patients with PHC indicates a poor prognosis.

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Section: Discussionmentioning

confidence: 99%

A Noval Established Cuproptosis-Associated LncRNA Signature for Prognosis Prediction in Primary Hepatic Carcinoma

Luo

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Pyroptosis refers to programmed cell death triggered by the inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis include cell swelling, membrane perforation and the release of cellular contents ( Rao et al, 2022 ). The classical pyroptosis pathway is mediated by the NLRP3/caspase-1/GSDMD pathway.…”

Section: Discussionmentioning

confidence: 99%

Aspirin in combination with gastrodin protects cardiac function and mitigates gastric mucosal injury in response to myocardial ischemia/reperfusion

et al. 2022

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Myocardial ischemia/reperfusion (I/R) injury after percutaneous coronary intervention (PCI) is common in acute myocardial infarction. Aspirin is commonly prescribed as anti-thrombotic therapy with coronary heart disease (CHD). However, long-term use of aspirin causes severe gastric mucosal damage. Gastrodin is a Chinese natural medicine with anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of combined therapy with aspirin and gastrodin on the myocardial and gastric mucosal injury in response to myocardial I/R injury and underlying mechanisms using the Sprague-Dawley (SD) rat model. Our results demonstrated that myocardial I/R caused significant cardiac dysfunction and gastric mucosal damage. Administration of aspirin led to significantly reduce myocardial infarction size and myocardial enzyme release, as well as significantly improved cardiac function through exerting anti-inflammatory effects. However, aspirin exacerbated gastric mucosal damage by increasing the levels of inflammatory mediators and endothelin (ET) while reducing prostaglandin E2 (PGE2) levels. The combined treatment with aspirin and gastrodin not only significantly protected gastric mucosa by normalizing the expression levels of the inflammatory factors, ET and PGE2, but also significantly reduced myocardial infarction size and improved cardiac function by inhibiting inflammation in response to I/R. The combination therapy also dramatically down-regulated the levels of pyroptosis-related proteins in the myocardium and gastric mucosa. The combination therapy showed obviously reduced level of thromboxane B2 (TXB2), which was simultaneously accompanied with increased levels of the tissue plasminogen activator (t-PA). This suggested that gastrodin did not inhibit the anti-thrombotic function of aspirin. Accordingly, aspirin in combination with gasrtodin protected the structural and functional integrity of the heart and stomach by suppressing pyroptosis and inflammation. Therefore, combination of aspirin and gastrodin is a promising treatment for cardiac dysfunction and gastric mucosa injury after myocardial I/R.

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“…Pyroptosis, as a new type of programmed cell necrosis, is mainly triggered by inflammasome and releases the intracellular inflammatory factors, and exerts tumor suppression function and evokes anti-tumor immunity responses (17,21,22). To further clarify the role of GALNT6 in PDAC, the effect of GALNT6 on PDAC pyroptosis was investigated.…”

Section: Galnt6 Promotes Inflammation and Pyroptosismentioning

confidence: 99%

Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway

Ding

Liu²,

Lv³

et al. 2023

Front. Oncol.

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BackgroundPancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) is frequently overexpressed in PDAC. However, the role of GALNT6 in the PDAC remains unclear.MethodsThe expression of GALNT6 in pancreatic cancer and normal tissues were analyzed by bioinformatic analyses and immunohistochemistry. CCK8 and colony formation were used to detect cell proliferation. Flow cytometry was applied to detect cell cycle.The pyroptosis was detected by scanning electron microscopy. The mRNA expression was detected by qRT-PCR. The protein expression and localization were detected by western blot and immunofluorescence assay. ELISA was used to detect the levels of inflammatory factors.ResultsThe expression of GALNT6 was associated with advanced tumor stage, and had an area under curve (AUC) value of 0.919 in pancreatic cancer based on the cancer genome atlas (TCGA) dataset. Knockdown of GALNT6 inhibited cell proliferation, migration, invasion and cell cycle arrest of PDAC cells. Meanwhile, knockdown of GALNT6 increased the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18), the release of inflammasome and an increasing of Gasdermin D (GSDMD), N-terminal of GSDMD (GSDMD-N), Gasdermin E (GSDME) and N-terminal of GSDME (GSDME-N) in PDAC cells. GALNT6 suppressed the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GSDMD by glycosylation of NF-κB and inhibiting the nucleus localization of NF-κB. Additionally, GALNT6 promotes the degradation of GSDME by O-glycosylation.ConclusionWe found that GALNT6 is highly expressed in pancreatic cancer and plays a carcinogenic role. The results suggested that GALNT6 regulates the pyroptosis of PDAC cells through NF-κB/NLRP3/GSDMD and GSDME signaling. Our study might provides novel insights into the roles of GALNT6 in PDAC progression.

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Pyroptosis in inflammatory diseases and cancer

Cited by 173 publications

References 125 publications

A Noval Established Cuproptosis-Associated LncRNA Signature for Prognosis Prediction in Primary Hepatic Carcinoma

A Noval Established Cuproptosis-Associated LncRNA Signature for Prognosis Prediction in Primary Hepatic Carcinoma

Aspirin in combination with gastrodin protects cardiac function and mitigates gastric mucosal injury in response to myocardial ischemia/reperfusion

Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway

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