Elevated intracellular cAMP concentration mediates growth suppression in glioma cells

Safitri, Dewi; Potter, H. Phelps; Harris, Matthew; Winfield, Ian J.; Kopanitsa, Liliya; Yeung, Ho Yan; Svensson, Fredrik; Rahman, Taufiq; Harper, Matthew T.; Bailey, David; Ladds, Graham

doi:10.1101/718601

Cited by 4 publications

(4 citation statements)

References 53 publications

(33 reference statements)

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“…Interestingly, the elevation of cAMP levels with forskolin induces cell cycle arrest of C6 glioma cells in the G 2 /M phase. In comparison, inhibition of PDEs not only inhibits cell growth via the cAMP/PKA cascade, but also triggers cell death through caspase-3/-7 activation ( Safitri et al, 2020 ). It is described that anticancer agents, such as RSV, may act by modulating cell cycle–associated proteins, such as cyclins, cyclin-dependent kinase (CDK), and CDK inhibitors ( Wolter et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Antitumoral Action of Resveratrol Through Adenosinergic Signaling in C6 Glioma Cells

et al. 2021

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Gliomas are the most common and aggressive primary tumors in the central nervous system. The nucleoside adenosine is considered to be one major constituent within the tumor microenvironment. The adenosine level mainly depends on two enzymatic activities: 5′-nucleotidase (5′NT or CD73) that synthesizes adenosine from AMP, and adenosine deaminase (ADA) that converts adenosine into inosine. Adenosine activates specific G-protein coupled receptors named A1, A2A, A2B, and A3 receptors. Resveratrol, a natural polyphenol present in grapes, peanuts, and berries, shows several healthy effects, including protection against cardiovascular, endocrine, and neurodegenerative diseases and cancer. However, the molecular mechanisms of resveratrol actions are not well known. Recently, we demonstrated that resveratrol acts as an agonist for adenosine receptors in rat C6 glioma cells. The present work aimed to investigate the involvement of adenosine metabolism and adenosine receptors in the molecular mechanisms underlying the antitumoral action of resveratrol. Results presented herein show that resveratrol was able to decrease cell numbers and viability and to reduce CD73 and ADA activities, leading to the increase of extracellular adenosine levels. Some resveratrol effects were reduced by the blockade of A1 or A3 receptors by DPCPX or MRS1220, respectively. These results suggest that reduced CD73 activity located in the plasma membrane in addition to a fine-tuned modulatory role of adenosine receptors could be involved, at least in part, in the antiproliferative action of resveratrol in C6 glioma cells.

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Section: Discussionmentioning

confidence: 99%

Antitumoral Action of Resveratrol Through Adenosinergic Signaling in C6 Glioma Cells

et al. 2021

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“…In addition, cells in the logarithmic phase were seeded into the 6-well plates and assigned into the Colforsin group (glioma cells were treated with 1.6 μM Colforsin) and the dimethyl sulfoxide (DMSO) group (cells were treated with an equivalent concentration of DMSO) [21]. DMSO and Colforsin were provided by MedChemExpress (HY-15371, Monmouth Junction, NJ, USA).…”

Section: Sample Collectionmentioning

confidence: 99%

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR-21-5p/CASKIN1/cAMP Axis

Dong

Yuemaierabola

et al. 2021

Oxidative Medicine and Cellular Longevity

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Glioma is a type of malignant intracranial tumor. Extensive research has identified the participation of long noncoding RNAs (lncRNAs) in glioma progression. This study investigated the mechanism of LINC00294 in mitochondrial function and glioma cell apoptosis. Glioma miRNA and mRNA microarray datasets were obtained, and differentially expressed lncRNAs in glioma were screened through various databases. The LINC00294 expression in glioma patients and glioma cells was detected. Glioma cells were treated under hypoxic conditions and transfected with LINC00294 silencing. The apoptosis and mitochondrial function of glioma cells were measured. The expressions of and relations among miR-21-5p, CASKIN1, and cAMP in glioma cells were analyzed. Under hypoxic conditions and LINC00294 silencing, the apoptosis and mitochondrial function of glioma cells were detected after inhibiting miR-21-5p or overexpressing CASKIN1. Our results indicated that LINC00294 was downregulated in glioma. LINC00294 silencing inhibited glioma cell apoptosis under hypoxia. LINC00294 silencing reversed the inhibition of hypoxia on mitochondrial function under hypoxia. LINC00294 promoted the CASKIN1 expression by sponging miR-21-5p and activated the cAMP pathway. Inhibition of miR-21-5p or overexpression of CASKIN1 annulled the effects of LINC00294 silencing on mitochondrial function and glioma cell apoptosis under hypoxia. In conclusion, LINC00294 elevated the CASKIN1 expression by sponging miR-21-5p and activating the cAMP signaling pathway, thus inhibiting mitochondrial function and facilitating glioma cell apoptosis.

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“…Through GO, KEGG, and ssGSEA analysis, we have a better understanding of classical cellular pathways with different expression patterns. GSEA analysis showed high PIM1 expression was related to representative BP including cell cycle, cAMP signaling pathway, Chemokine signaling pathway, Cytokinecytokine receptor interaction, Glutomatergic synapse, IL-17 signaling pathway, Necroptosis, Neutrophil extracellular trap formation, Transcriptional misregulation in cancer, et al The abnormal activation of key signaling pathways, cAMP [19], Chemokine [20], Cytokine-cytokine receptor interaction [21], glutamatergic synapse [22], IL-17 signaling pathway [23], RIPK3 [24]have been connected to the development of glioma. We further con rmed with cellular experiments that inhibiting PIM expression increased caspase 3 activity thereby inhibit LGG malignant progression.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of high-level PIM1 and is related to tumor microenvironment in Low-grade Glioma

Chen

Huang

Zhong

et al. 2022

Preprint

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PIM1 has been shown to be associated with the development of multiple human cancers, but the biological mechanisms of PIM1 in glioma development, particularly the role of TME immune cell infiltration, remain unclear. We analyzed clinical information and gene expression data of all glioma samples and evaluated the relationship with overall survival by univariate and multivariate Cox regression. We also analyzed genes and downstream signaling pathways associated with PIM1 by gene set enrichment analysis. And we analyzed characterized oncogenic pathways, biological pathways, and TME immune cell infiltration in glioma samples with different PIM1 expressions, and validated it by in vitro experiments. The results of Cox regression analysis confirmed that overexpression of PIM1 was significantly associated with malignant progression and poorer survival of gliomas. Using PIM1 and other clinical features, we successfully constructed a nomogram to predict the prognosis of glioma, and Gene Set Enrichment Analysis revealed the association between PIM1 overexpression with cell cycle, cAMP signaling pathway, et al. Meanwhile, overexpression of PIM1 was significantly associated with increased expression of many immune checkpoints and immune cell infiltration. In conclusion, our study confirmed that overexpression of PIM1 is a potential molecular marker of poor prognosis in glioma and that PIM1 plays an important role in TME immune cell infiltration. By identifying PIM1-regulated signaling pathways and immune checkpoints enhances our understanding of the TME immune cell infiltration characteristics of glioma and contributes to the development of immunotherapeutic strategies.

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Elevated intracellular cAMP concentration mediates growth suppression in glioma cells

Cited by 4 publications

References 53 publications

Antitumoral Action of Resveratrol Through Adenosinergic Signaling in C6 Glioma Cells

Antitumoral Action of Resveratrol Through Adenosinergic Signaling in C6 Glioma Cells

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR-21-5p/CASKIN1/cAMP Axis

Prognostic significance of high-level PIM1 and is related to tumor microenvironment in Low-grade Glioma

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