NLRP3 inflammasome inactivation driven by miR‑223‑3p reduces tumor growth and increases anticancer immunity in breast cancer

Zhang, Liping; Li, Hongzhi; Zang, Yuwei; Wang, Rui

doi:10.3892/mmr.2019.9889

Cited by 33 publications

(47 citation statements)

References 35 publications

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“…MiR-223-3p mimics suppressed NLRP3 expression, leading to an increased apoptotic rate and reduced proliferative capacity and ASC, IL-1β, and IL-18 expression levels. Consistent with "in vitro" results, "in vivo" experiments demonstrated that miR-223-3p reduced tumor growth and increased survival rate in mice (76). Collectively, these data indicate that targeting the inflammasome/IL-1 pathway with a miR-223-3p-like molecule could suppress the growth of BC cells by inactivation of the NLRP3 inflammasome.…”

Section: Inflammasomes and Bcsupporting

confidence: 80%

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NLRP3 Inflammasome From Bench to Bedside: New Perspectives for Triple Negative Breast Cancer

et al. 2020

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The tumor microenvironment (TME) is crucial in cancer onset, progression and response to treatment. It is characterized by an intricate interaction of immune cells and cytokines involved in tumor development. Among these, inflammasomes are oligomeric molecular platforms and play a key role in inflammatory response and immunity. Inflammasome activation is initiated upon triggering of pattern recognition receptors (Toll-like receptors, NOD-like receptors, and Absent in melanoma like receptors), on the surface of immune cells with the recruitment of caspase-1 by an adaptor apoptosis-associated specklike protein. This structure leads to the activation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and participates in different biological processes exerting its effects. To date, the Nod-Like Receptor Protein 3 (NLRP3) inflammasome has been well studied and its involvement has been established in different cancer diseases. In this review, we discuss the structure, biology and mechanisms of inflammasomes with a special focus on the specific role of NLRP3 in breast cancer (BC) and in the subgroup of triple negative BC. The NLRP3 inflammasome and its downstream pathways could be considered novel potential tumor biomarkers and could open new frontiers in BC treatment.

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Section: Inflammasomes and Bcsupporting

confidence: 80%

“…Zhang and colleagues showed that microRNA-223-3p (miR-223-3p) had an inhibiting effect on the NLRP3 pathways (76). Previous studies had already considered that MiR-223-3p may be involved in the regulation of inflammatory response, immunosuppression, cell growth and angiogenesis in different cancer cells (77,78).…”

Section: Inflammasomes and Bcmentioning

confidence: 99%

NLRP3 Inflammasome From Bench to Bedside: New Perspectives for Triple Negative Breast Cancer

et al. 2020

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“…NLRP3 inflammasome could represent a novel potential target for the treatment of breast cancer [ 56 ]. In a recent preclinical study, the pharmacological inhibition of NLRP3 through miRNA reduced the tumor growth and the immune-resistance in breast cancer-bearing mice through ASC/IL-1/IL-18 pathways; these data provide new clinical insights for breast cancer management [ 57 ]. Notably, NLRP3 is associated with myocardial injuries, atherosclerosis, and diabetes mellitus [ 57 ]; high glucose stimulates NLRP3 expression thorough inhibition of its ubiquitinization in human cells [ 57 ]; therefore, we can speculate that hyperglycemia could enhance cardiotoxicity and responsiveness to ipilimumab through the NLRP3 complex.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

Quagliariello

Laurentiis

Cocco

et al. 2020

IJMS

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Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.

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“…Interestingly, in-depth molecular studies [ 129 – 131 ] concluded that noncoding molecules such as miRNA are able to inhibit the activity of inflammasomes. It was found that miRNA-223 molecule binds to the 3′-UTR of NLRP3 mRNA and suppresses its protein expression, therefore blocking the priming and the production of IL-1 β [ 132 ].…”

Section: Molecular Inflammatory Events During Cancer Development Amentioning

confidence: 99%

Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis

Balahura

Șelaru

Dinescu

et al. 2020

Journal of Immunology Research

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Over the past decade, it has been well established that tumorigenesis is affected by chronic inflammation. During this event, proinflammatory cytokines are produced by numerous types of cells, such as fibroblasts, endothelial cells, macrophages, and tumor cells, and are able to promote the initiation, progression, and metastasis of different types of cancer. When persistent inflammation occurs, activation of inflammasome complexes is initiated, leading to its assembly and further activation of caspase, production of proinflammatory cytokines, and pyroptosis induction. The function of this multiprotein complex is not only to reassure inflammation and to promote cell death, through caspase activity, but also has been identified to have significant contributions during tumorigenesis and cancer development. So far, many efforts have been made in order to extend the knowledge of inflammasome implications and how its components could be targeted as therapeutic agents. Additionally, microRNAs (miRNAs), evolutionary conserved noncoding molecules, have emerged as pivotal players during numerous biological events by regulating gene and protein expression. Therefore, dysregulations of miRNA expressions have been correlated with inflammation during tumor development. In this review, we aim to highlight the dual role of inflammasomes and proinflammatory cytokines during carcinogenesis paired with the distinguished effects of miRNAs upon inflammation cascades during tumor growth and progression.

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NLRP3 inflammasome inactivation driven by miR‑223‑3p reduces tumor growth and increases anticancer immunity in breast cancer

Cited by 33 publications

References 35 publications

NLRP3 Inflammasome From Bench to Bedside: New Perspectives for Triple Negative Breast Cancer

NLRP3 Inflammasome From Bench to Bedside: New Perspectives for Triple Negative Breast Cancer

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis

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