ASC deficiency suppresses proliferation and prevents medulloblastoma incidence

Knight, Elizabeth R.W.; Patel, Esita; Flowers, Cornelius; Crowther, Andrew; Miller, C. Ryan; Gershon, Timothy R.; Deshmukh, Mohanish

doi:10.1038/onc.2013.577

Cited by 10 publications

(8 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found that overexpression of PYCARD significantly promoted cell proliferation and migration ability after TMZ treatment; conversely, the loss of PYCARD decreased cell proliferation and migration ability. However, no noticeable apoptotic and half-maximal inhibitory concentration (IC 50 ) changes were observed in our research (30)(31)(32)(33). This is inconsistent with the previous results (32), and this discrepancy is due to cancer heterogeneity and the complex network regulating mRNA.…”

Section: Discussioncontrasting

confidence: 99%

“…Recent studies have found PYCARD deficiency suppresses proliferation and prevents medulloblastoma incidence (30). We also found that overexpression of PYCARD significantly promoted cell proliferation and migration ability after TMZ treatment; conversely, the loss of PYCARD decreased cell proliferation and migration ability.…”

Section: Discussionsupporting

confidence: 60%

“…Previous studies have shown that PYCARD is inhibitor by DNA methylation in human breast tumors (36). Aberrant methylation and down-regulation of PYCARD by DNA methyltransferase 1 (Dnmt1), Dnmt3b and Dnmt1/ Dnmt3a in human glioblastoma (30,(37)(38)(39)(40). However, the detailed molecular mechanism behinds the resistance remains unclear, and further research to explore this area is warranted.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma

Liang

Zhong

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: PYD and CARD domain-containing (PYCARD) was upregulated in TMZ-resistant cell lines and glioma tissue and was correlated with poor prognosis, its role in glioma is unclear known. The aim of this study was to elucidate the relationship between PYCARD and glioma based on Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) databases.Methods: Glioma-resistant cells were compared with parental cells based on the GSE53014 and GSE113510 data sets. The relationship between PYCARD, tumor microenvironment, and long noncoding RNAs (lncRNAs) was assessed using logistic regression. Moreover, Kaplan-Meier and Cox regression were used to analyze the relationship between PYCARD expression and survival rate. Gene set enrichment analysis (GSEA) was also used to determine the biological function of PYCARD and lncRNAs. Cell viability and cell migration assays were used to evaluate the ability of cells to migrate and proliferate. Finally, we analyzed the expression patterns of PYCARD genes in a wide range of cancers.Results: Elevated expression of PYCARD promoted glioma cell proliferation and migration. PYCARD expression was significantly positively associated with gamma delta T cells but negatively correlated with M2 macrophages in glioblastoma multiforme (GBM). Likewise, PYCARD expression was significantly positively associated with monocytes but negatively associated with activated mast cells in low grade glioma (LGG).We also found that 3 PYCARD-related lncRNAs in GBM and 4 PYCARD-related lncRNAs in LGG had a predictive value for glioma patients. The pan-cancer analysis showed that PYCARD expression was higher in most cancer groups.Conclusions: High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma

Liang

Zhong

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…In agreement with a tumor suppressor function, ASC methylation correlated with poor prognosis in non-small-cell lung cancer [39], oral squamous cell carcinoma [40] and gastric cancer [41]. On the other hand, in another study [42], high expression of ASC in oral cavity squamous cell carcinoma correlated with poor patients’ survival and in a medulloblastoma mouse model ASC genetic deletion markedly reduced proliferation, hyperplasia and mortality [43]. In addition, in myeloid cells ASC, as an inflammasome adaptor molecule, is required for IL-1β processing and activation.…”

Section: Discussionmentioning

confidence: 88%

The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer

Brunetto

Monte

Balzano

et al. 2019

j. immunotherapy cancer

View full text Add to dashboard Cite

BackgroundThe thymic stromal lymphopoietin (TSLP), a key cytokine for development of Th2 immunity, is produced by cancer associated fibroblasts (CAFs) in pancreatic cancer where predominant tumor infiltrating Th2 over Th1 cells correlates with reduced patients’ survival. Which cells and molecules are mostly relevant in driving TSLP secretion by CAFs in pancreatic cancer is not defined.MethodsWe performed in vitro, in vivo and ex-vivo analyses. For in vitro studies we used pancreatic cancer cell lines, primary CAFs cultures, and THP1 cells. TSLP secretion by CAFs was used as a read-out system to identify in vitro relevant tumor-derived inflammatory cytokines and molecules. For in vivo studies human pancreatic cancer cells and CAFs were orthotopically injected in immunodeficient mice. For ex-vivo studies immunohistochemistry was performed to detect ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression in surgical samples. Bioinformatics was applied to interrogate published data sets.ResultsWe show in vitro that IL-1α and IL-1β released by pancreatic cancer cells and tumor cell-conditioned macrophages are crucial for TSLP secretion by CAFs. Treatment of immunodeficient mice orthotopically injected with human IL-1 positive pancreatic cancer cells plus CAFs using the IL-1R antagonist anakinra significantly reduced TSLP expression in the tumor. Importantly, we found that pancreatic cancer cells release alarmins, among which ASC, able to induce IL-1β secretion in macrophages. The relevance of ASC was confirmed ex-vivo by its expression in both tumor cells and tumor associated macrophages in pancreatic cancer surgical samples and survival data analyses showing statistically significant inverse correlation between ASC expression and survival in pancreatic cancer patients.ConclusionsOur findings indicate that tumor released IL-1α and IL-1β and ASC are key regulators of TSLP secretion by CAFs and their targeting should ultimately dampen Th2 inflammation and improve overall survival in pancreatic cancer.Electronic supplementary materialThe online version of this article (10.1186/s40425-019-0521-4) contains supplementary material, which is available to authorized users.

show abstract

“…Moreover, knockdown of SMAD5 by overexpressing the miR-155 expression enhanced the aggressiveness of diffuse large B cell lymphoma in vivo [ 52 ]. On the other hand , increased expression of SMAD5 was found to reduce proliferation of cerebellar granule neuron progenitors [ 53 ],and induce apoptosis which may have a negative impact on the proliferative activity of the cells [ 54 ]. As far as MSK1 is concerned, inhibition of MSK1 resulted in a marked increase in cell production during mouse pancreatic development [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-130b is involved in bovine granulosa and cumulus cells function, oocyte maturation and blastocyst formation

et al. 2017

View full text Add to dashboard Cite

BackgroundOocyte maturation and preimplantation embryo development are controlled by array of genes that are post-transcriptionally regulated by microRNAs. With respect to this, previously, we identified altered expression of microRNA-130b (miR-130b) during oocyte maturation. Here, we aimed to investigate the role of miR-130b in bovine granulosa and cumulus cell function, oocyte maturation and preimplantation embryo development using gain- and loss-of- function approach.MethodsFor this study, the granulosa cells, cumulus cells and the oocytes were collected from ovaries obtained from slaughterhouse. The genes targeted by miR-130b were identified using dual-luciferase reporter assay. The role of miR-130b in granulosa and cumulus cell function was investigated by increasing and inhibiting its expression in in vitro cultured cells using miR-130b precursor and inhibitor, respectively while the role of miR-130b on oocyte development, immature oocytes were microinjected with miR-130b precursor and inhibitor and the polar body extrusion, the proportion of oocytes reaching to metaphase II stage and the mitochondrial were determined in each oocyte group 22 h after microinjection. Moreover, to investigate the role of miR-130b during preimplantation embryo development, zygote stage embryos were microinjected with miR-130b precursor or inhibitor and the cleavage rate, morula and blastocyst formation was analyzed in embryos derived from each zygote group after in vitro culture.ResultsThe luciferase assay showed that SMAD5 and MSK1 genes were identified as the direct targets of miR-130b. Overexpression of miR-130b increased the granulosa and cumulus cell proliferation, while inhibition showed the opposite phenotype. Apart from these, modulation of miR-130b altered the lactate production and cholesterol biosynthesis in cumulus cells. Furthermore, inhibition of miR-130b expression during oocyte in vitro maturation reduced the first polar body extrusion, the proportion of oocytes reaching to metaphase II stage and the mitochondrial activity, while inhibition of miR-130b during preimplantation embryo development significantly reduced morula and blastocyst formation.ConclusionThis study demonstrated that in vitro functional modulation of miR-130b affected granulosa and cumulus cell proliferation and survival, oocyte maturation, morula and blastocyst formation suggesting that miR-130b is involved in bovine oocyte maturation and preimplantation embryo development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-017-0336-1) contains supplementary material, which is available to authorized users.

show abstract

ASC deficiency suppresses proliferation and prevents medulloblastoma incidence

Cited by 10 publications

References 44 publications

High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma

High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma

The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer

MicroRNA-130b is involved in bovine granulosa and cumulus cells function, oocyte maturation and blastocyst formation

Contact Info

Product

Resources

About