E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells

Wei, Qing; Zhu, Rui; Zhu, Jun; Zhao, Rongping; Li, Min

doi:10.3727/096504018x15462920753012

Cited by 124 publications

(100 citation statements)

References 25 publications

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“…Several of the genes co-expressed with MIR22HG, including NLRP3, CSF1R, SIGLEC10, and ZEB2, were reported to play crucial roles in the initiation and progression of HCC. [28][29][30][31] Functional analysis of the coexpressed genes suggested a significant enrichment in molecular functions that included protein tyrosine kinase activity, non-membrane spanning protein tyrosine kinase activity, and phosphotyrosine residue binding, as well as activation of pathways involving hematopoietic cell lineage, viral protein interaction with cytokines and cytokine receptors, and activity of the Rap1 signaling Figure 10 Heatmap of differentially expressed lncRNAs in nitidine chloride-treated hepatocellular carcinoma (HCC) xenografts The expression changes of differentially expressed lncRNAs between before and after nitidine chloride treatment in HCC xenografts are displayed in squares of colors ranging from green to red.…”

Section: Dovepressmentioning

confidence: 99%

MIR22HG As A Tumor Suppressive lncRNA In HCC: A Comprehensive Analysis Integrating RT-qPCR, mRNA-Seq, And Microarrays

Xiong

et al. 2019

OTT

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Introduction: MIR22HG has a reported involvement in the tumorigenesis of a variety of cancers, including hepatocellular carcinoma (HCC). However, the exact molecular mechanism of MIR22HG in HCC has not been clarified. Methods: In the present study, we integrated data from in-house RT-qPCR, RNA-sequencing, microarray, and literature studies to conduct a comprehensive evaluation of the clinicopathological and prognostic significance of MIR22HG in an extremely large group of HCC samples. We also explored the potential mechanism of MIR22HG in HCC by analyzing the alteration profiles of MIR22HG in HCC to predict transcription factors (TFs) that may interact with MIR22HG and to annotate the biological functions of genes co-expressed with MIR22HG. MIR22HG expression was also compared in HCC nude mice xenografts before and after a treatment with nitidine chloride. Results: We found that MIR22HG was downregulated in HCC and that this downregulation correlated with the malignant phenotype of HCC. Comprehensive analysis of the prognostic impact of MIR22HG in HCC revealed a beneficial effect of MIR22HG on the survival outcome of HCC patients. Seven cases of MIR22HG deep deletion occurred in 360 of the cancer genome atlas (TCGA) provisional HCC samples. A total of 22 MIR22HG-TF-mRNA triplets in HCC were predicted by the lncRNAmap. Co-expressed genes of MIR22HG, identified by weighted correlation network analysis (WGCNA), mainly participated in the pathways involving osteoclast differentiation, chemokine signaling pathways, and hematopoietic cell lineage. In vivo experiments demonstrated that nitidine chloride could stimulate MIR22HG expression in HCC xenografts. Conclusion: In summary, MIR22HG may play a tumor-suppressive role in HCC by coordinating with predicted TFs and co-expressed genes, such as NLRP3, CSF1R, SIGLEC10, and ZEB2, or by being controlled by nitidine chloride.

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Section: Dovepressmentioning

confidence: 99%

MIR22HG As A Tumor Suppressive lncRNA In HCC: A Comprehensive Analysis Integrating RT-qPCR, mRNA-Seq, And Microarrays

Xiong

et al. 2019

OTT

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“…The gasdermin (GSDM) family has regulatory functions in normal cell proliferation and differentiation 23,24 and include gasdermin A (GSDMA), gasdermin B (GSDMB), gasdermin C (GSDMC), gasdermin D (GSDMD), gasdermin E (GSDME), and DFNB59. [25][26][27] GSDMA and GSDMB genes are located at 17q2, while GSDMC and GSDMD are located at 8q24. 28 With the exception of DFNB59, these gene family members share about 45% sequence homology, and all of the GSDM have two domains that are capable of binding to each other and are connected by a long flexible linker.…”

Section: Introductionmentioning

confidence: 99%

Role of GSDMB in Pyroptosis and Cancer

Li¹,

Li²,

Bai³

2020

CMAR

101

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Gasdermin B (GSDMB) belongs to the gasdermin (GSDM) family which may adopt different mechanisms of intramolecular domain interactions to modulate their lipidbinding and pore-forming activities. The GSDM family has regulatory functions in cell proliferation and differentiation, especially in pyroptosis process. Pyroptosis is a proinflammatory form of regulated cell death and is designed to attract a nonspecific innate response to the site of infection. For cancer cells, the activation of pyroptosis may promote cell death and exert anticancer properties. Also, recent studies have observed the pyroptosislike features in GSDMB and some researches have shown that GSDMB overexpression occurred in several kinds of cancers; these findings bring a contradiction with the participation of GSDMB in pyroptosis. Although people pay less attention to GSDMB, it still has some essential research value. It is a paradox that GSDMB might participate in programmed cell death, which might put forward a research direction of therapeutic targets for cancer. Here, we review the possible progress of how GSDMB participated in this inflammatory regulation mechanistically and the potential functions of GSDMB in cancer.

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“…4h). The presence of morphological structures, termed pyroptotic bodies, in cells undergoing E2 stimulation has been reported 47 . Pyroptotic bodies show a similar diameter (1-5 μm) to apoptotic bodies.…”

Section: Estradiol Promotes Mmp-3 Secretion By Mcf-10a Cells and Basmentioning

confidence: 99%

Estradiol/GPER affects the integrity of mammary duct-like structures in vitro

Deng

Miki

Nakanishi

2020

Sci Rep

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High estrogen concentration leads to an inflammatory reaction in the mammary gland tissue in vivo;however, the detailed mechanism underlying its specific effects on the breast duct has not been fully clarified. We used 3D-cultured MCF-10A acini as a breast duct model and demonstrated various deleterious effects of 17-β estradiol (E2), including the destruction of the basement membrane surrounding the acini, abnormal adhesion between cells, and cell death via apoptosis and pyroptosis. Moreover, we clarified the mechanism underlying these phenomena: E2 binds to GPER in MCF-10A cells and stimulates matrix metalloproteinase 3 (MMP-3) and interleukin-1β (IL-1β) secretion via JNK and p38 MAPK signaling pathways. IL-1β activates the IL-1R1 signaling pathway and induces continuous MMP-3 and IL-1β secretion. Collectively, our novel findings reveal an important molecular mechanism underlying the effects of E2 on the integrity of duct-like structures in vitro. Thus, E2 may act as a trigger for ductal carcinoma transition in situ.Estrogens are female hormones secreted mainly by ovaries. They serve diverse functions in the female reproductive organs (e.g., uterus and mammary gland) as well as bones, blood vessels, nerves, and brain 1-4 . Estrogens comprise three types: estrone (E1), 17-β estradiol (E2), and estriol (E3) 5 . E2 binds to estrogen receptors α and β, and the complex formed migrates to DNA of the target gene to activate its transcription 6 . In addition to these classic transcriptional mechanisms, G-protein-coupled receptor 30 (GPER) is an estrogen receptor involved in nongenomic mechanisms 7,8 . GPER expression is tissue-specific, with high expression found in the reproductive system, heart, intestine, ovary, CNS, pancreatic islets, adipose tissue, and neurons. And abnormal GPER expression is associated with depression, hypertension, diabetes, and osteoporosis 9-11 . Also, high GPER expression in breast cancer is associated with increased recurrence 12,13 . Estrogen action via GPER leads to enhanced fibronectin matrix assembly in breast cancer cells 14 . An important biological consequence of GPER activation is the regulation of cell growth and apoptotic cell death 15,16 . In this process, E2 binding to GPER causes G-protein complex dissociation 17,18 , and then the βγ subunit activates the tyrosine kinase Src, which leads to the activation of MAPK pathway 17,18 . GPER activation further activates the downstream signaling molecules such as MAPK and PI3K/ AKT 19,20 .In this study, 3D cultured MCF-10A acini were exposed to E2, which led to the disruption of basement membrane and cell death of some ductal cells. And we further revealed the underlying mechanism in which E2 binding to GPER resulted in cAMP-mediated activation of c-jun N-terminal kinase (JNK) and p38 MAPK signaling pathway, followed by interleukin 1β (IL-1β) and matrix metalloproteinase-3 (MMP-3) expression and secretion. Results Estradiol induces basement membrane disruption in MCF-10A acini.We constructed a 3D model using the immortalized non-transfo...

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E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells

Cited by 124 publications

References 25 publications

<p>MIR22HG As A Tumor Suppressive lncRNA In HCC: A Comprehensive Analysis Integrating RT-qPCR, mRNA-Seq, And Microarrays</p>

<p>MIR22HG As A Tumor Suppressive lncRNA In HCC: A Comprehensive Analysis Integrating RT-qPCR, mRNA-Seq, And Microarrays</p>

<p>Role of GSDMB in Pyroptosis and Cancer</p>

Estradiol/GPER affects the integrity of mammary duct-like structures in vitro

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