An update on the regulatory mechanisms of NLRP3 inflammasome activation

Cellular and Molecular Immunology, Год журнала: 2021, Номер 18(5), С. 1141 - 1160

Опубликована: Апрель 13, 2021

Abstract The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β triggering pyroptosis, which paramount importance variety physiological pathological conditions. Over past decade, considerable advances have been made elucidating molecular mechanisms underlying priming/licensing (Signal 1) assembly 2) NLRP3 activation. Recently, number studies indicated that step regulated by complicated at both transcriptional posttranslational levels. In this review, we discuss current understanding mechanistic details activation with particular emphasis on protein-protein interactions, modifications, spatiotemporal regulation machinery. We also present detailed summary multiple positive and/or negative regulatory pathways providing upstream signals culminate assembly. A better will provide opportunities for development methods prevention treatment inflammasome-related diseases.

Язык: Английский

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Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer

International Journal of Biological Sciences, Год журнала: 2021, Номер 17(10), С. 2606 - 2621

Опубликована: Янв. 1, 2021

Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown.Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis.Nevertheless, whether pyroptosis contributes DDP-induced effect TNBC unexploited.In present study, NLRP3/caspase-1/GSDMD pathway involved of vitro and vivo, providing DDP might induce TNBC.Moreover, activated up-regulating long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3).Furthermore, knockdown MEG3 not only partly abolished activation on pathway-mediated pyroptosis, but also reversed suppression tumor growth metastasis ability further confirming may partially mediate pyroptotic signaling upon treatment.Thus, our data uncovered a novel induced via MEG3/NLRP3/caspase-1/GSDMD exert effects, which help develop new strategies for therapeutic interventions TNBC.

Язык: Английский

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Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects

Phytotherapy Research, Год журнала: 2021, Номер 36(1), С. 189 - 213

Опубликована: Окт. 25, 2021

Abstract Curcumin is a phytochemical isolated from Curcuma longa with potent tumor‐suppressor activity, which has shown significant efficacy in pre‐clinical and clinical studies. stimulates cell death, triggers cycle arrest, suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) DNA damage apoptosis chemotherapy. However, CP adverse effects on several organs of the body, drug resistance frequently observed. The purpose present review to show function curcumin decreasing CP's impacts improving its antitumor activity. administration reduces ROS levels prevent normal cells. Furthermore, can inhibit inflammation via down‐regulation NF‐κB maintain organs. nanoformulations reduce hepatoxicity, neurotoxicity, renal toxicity, ototoxicity, cardiotoxicity caused by CP. Notably, potentiates cytotoxicity mediating death arrest. Besides, STAT3 NF‐ĸB as tumor‐promoting enhance sensitivity resistance. targeted delivery tumor cells be mediated nanostructures. In addition, derivatives are also able CP‐mediated side effects, increase against various types.

Язык: Английский

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Emerging mechanisms of pyroptosis and its therapeutic strategy in cancer

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Июль 27, 2022

Abstract Pyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage gasdermin family proteins. Based on accumulating evidence, pyroptosis closely associated with tumour development, but the molecular mechanism underlying activation and signalling pathways regulated remain unclear. In this review, we first briefly introduce definition, morphological characteristics, effect anticancer immunity. Then review recent progress concerning complex role in various tumours. Importantly, summarise FDA-approved chemotherapy drugs or natural compounds that exerted antitumor properties inducing cancer cells. Moreover, also focus current application nanotechnology-induced therapy. addition, some unsolved problems potential future research directions are raised.

Язык: Английский

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Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Авг. 17, 2022

Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with potential effectively extend patient survival. However, development drug resistance seriously limits clinical efficiency ultimately results in treatment failure death. A large number studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long RNAs, circular are widely involved regulation resistance. Their dysregulation contributes by modulating expression specific target genes cellular apoptosis, autophagy, efflux, epithelial-to-mesenchymal transition (EMT), stem cells (CSCs). Moreover, some ncRNAs also possess great as efficient, biomarkers diagnosis prognosis well targets patients. In this review, we summarize recent findings on emerging role underlying mechanisms focus their applications treatment. This information will be benefit early prognostic assessments ncRNA-based strategies

Язык: Английский

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Long non-coding RNAs and JAK/STAT signaling pathway regulation in colorectal cancer development

Frontiers in Genetics, Год журнала: 2023, Номер 14

Опубликована: Ноя. 29, 2023

Colorectal cancer (CRC) is one of the main fatal cancers. Cell signaling such as Janus kinase/signal transducer and activator transcription (JAK/STAT) substantially influences process gene expression cell growth. Long non-coding RNAs (lncRNAs) play regulatory roles in signaling, proliferation, fate. Hence, lncRNAs can be considered biomarkers The inhibitory or activating effects different on JAK/STAT pathway regulate proliferation tumor suppression. Additionally, immune responses which a role immunotherapy. Mechanisms CRC via regulation mainly include invasion, metastasis, apoptosis, adhesion, control inflammation. More profound findings are warranted to specifically target terms activation suppression hindering proliferation. Here, understand lncRNA cross-talk through pathway, we collected related vitro vivo data. Future insights may pave way for development novel diagnostic tools, therapeutic interventions, personalized treatment strategies patients.

Язык: Английский

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Pyroptosis in health and disease: mechanisms, regulation and clinical perspective

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 20, 2024

Язык: Английский

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A novel pyroptosis-related lncRNA signature for prognostic prediction in patients with lung adenocarcinoma

Bioengineered, Год журнала: 2021, Номер 12(1), С. 5932 - 5949

Опубликована: Янв. 1, 2021

Lung adenocarcinoma (LUAD) has been the major cause of tumor-associated mortality in recent years and a poor prognosis. Pyroptosis is regulated via activation inflammasomes participates tumorigenesis. However, effects pyroptosis-related lncRNAs (PRlncRNAs) on LUAD have not yet completely elucidated. Therefore, we attempted to systematically explore patterns cell pyroptosis establish novel signature for predicting survival. Based TCGA database, set up prognostic model by incorporating PRlncRNAs with differential expression using Cox regression LASSO regression. Kaplan–Meier analysis was conducted compare survival patients. We further simplified risk created nomogram enhance prediction Altogether, 84 were discovered. Subsequently, new constructed based five PRlncRNAs, GSEC, FAM83A-AS1, AL606489.1, AL034397.3 AC010980.2. The proposed exhibited good performance related immunocyte infiltration. exactly forecasted overall patients had excellent clinical utility. In present study, five-lncRNA are trustworthy effective indicators prognosis LUAD.

Язык: Английский

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Induction of Pyroptosis: A Promising Strategy for Cancer Treatment

Frontiers in Oncology, Год журнала: 2021, Номер 11

Опубликована: Фев. 26, 2021

Pyroptosis, a lytic pro-inflammatory type of programmed cell death, has been widely studied in diverse inflammatory disease models. Membrane perforation and swelling induced by cleaved gasdermin family members is the main characteristic pyroptosis. Emerging evidence revealed complicated relationship between pyroptosis cancer. On one hand, as provides comfortable environment for tumor proliferation. other excessive activation can inhibit development cells. In this review, we first summarized latest progress about molecular mechanism Then, from family, central molecules which formed pores on membrane, were highlighted. second part drugs that different tumors their concrete mechanisms based recent literature reports. final section, discussed several hotspots cancer therapy, will point out direction sequent research. brief, inducing cells promising strategy therapy.

Язык: Английский

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GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy

Expert Reviews in Molecular Medicine, Год журнала: 2021, Номер 23

Опубликована: Янв. 1, 2021

Pyroptosis is a recently identified mechanism of programmed cell death related to Caspase-1 that triggers series inflammatory reactions by releasing several proinflammatory factors such as IL-1β and IL-18. The process characterised the rupture membranes release contents through mediation gasdermin (GSDM) proteins. GSDMD an important member GSDM family plays critical role in two pathways pyroptosis. Diabetic nephropathy (DN) microvascular complication diabetes major cause end-stage renal disease. Recently, it was revealed GSDMD-mediated pyroptosis occurrence development DN. In this review, we focus on types kidney cells, tubular epithelial cells podocytes, illustrate DN provide new ideas for prevention, early diagnosis molecular therapy

Язык: Английский

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