&lt;p&gt;Rap2c as a Novel Biomarker for Predicting Poor Prognosis in Glioma&lt;/p&gt;

Wang, Xiucun; Wang, Cheng; Lin, Xiao; Yu, Zhengquan

doi:10.2147/ott.s247731

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…Altered ATRX and RAP2C have been reported to be associated with occurrence of gliomas. 48, 49 However, further studies are needed to explore association of miR-145-3p and these genes in neuroinflammation in AMN and cALD astrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, comparative IPA network analysis of CTL vs AMN showed that miR-145-3p is associated with HAND1, ATRX, and RAP2C genes. Altered ATRX and RAP2C have been reported to be associated with gliomas (Alghamri et al ., 2021; Wang X, 2020). However, further studies are needed to explore the association of miR-145-3p and these genes in X-ALD.…”

Section: Discussionmentioning

confidence: 99%

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iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy

Parasar

Kaur

Poisson

et al. 2022

Preprint

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Objective: The role of astrocytes largely remains to be explored in X-linked adrenoleukodystrophy (X-ALD). Due to limited study models and inaccessibility to patient-tissue samples, we differentiated astrocytes from patient fibroblast-derived induced pluripotent stem cell (iPSCs) which provided a unique system to investigate molecular and etiopathogenetic mechanisms, identify targets, and develop therapeutic agents for X-ALD. Methods: We reprogrammed fibroblasts from adrenomyeloneuropathy (AMN) and cerebral adrenoleukodystrophy (cALD) patients carrying ABCD1 with pathogenic variants and a control patient to generate iPSCs. We differentiated iPSCs into astrocytes and performed transmission electron microscopy, gene expression, immunoblotting, enzyme-linked immunosorbent assay, miRNA-Seq, and lipidomics to characterize phenotypic and molecular features of patient-derived astrocytes. Results: These differentiated astrocytes exhibit diseased phenotypes and replicate biochemical and molecular changes found in patients. We confirmed the deletion of ABCD1 gene-encoded ALD protein and identified ABCD1 variant-driven very long chain fatty acid deposition in AMN and cALD astrocytes. Especially, cALD astrocytes showed increased glycolysis, increased signal transducer and transcription activator (STAT)3 activation, higher miR-9 expression in miRNA-Seq analysis, and reduced expression of anti-inflammatory cytokines such as arginase-1 and mannose receptor C-type-1. Consequently, Toll-like receptor-signaling via myeloid differentiation primary response gene 88 (MyD88) and nuclear factor-kappa B (NF-κB; p52 and p65) induced STAT3 and an altered miR-9 expression is a potential contributor to inflammatory milieu in cALD while interleukin-6 -induced anti-inflammatory cytokine production and increased chemotactic CCL-2 (MCP-1) production in AMN potentially favors microglial recruitment protecting its further progression. Interpretation: We demonstrate for the first time that patient iPSC-derived astrocytes mimic and recapitulate neuroinflammatory and biochemical defects of X-ALD and provide an in vitro cellular system to study X-ALD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy

Parasar

Kaur

Poisson

et al. 2022

Preprint

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“…Current existing therapy for malignant glioma is a combination of chemotherapy and radiotherapy [ 5 ]. Despite attempts to improve treatment protocols, glioma patients still suffer from a low 5-year survival rate, reported to be as low as 5.5%, with a median survival period of 14.5–16.6 months [ 6 ]. Glioma stem cells (GSCs) have been implicated in tumor regrowth of glioma which is often treatment-resistant [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Transcription factor SNAI2 exerts pro-tumorigenic effects on glioma stem cells via PHLPP2-mediated Akt pathway

Peng

Chen

et al. 2022

Cell Death Dis

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The current study aimed to investigate the effects associated with SNAI2 on the proliferation of glioma stem cells (GSCs) to elucidate its underlying molecular mechanism in the development of glioma. The expression of Snail family transcriptional repressor 2 (SNAI2) in glioma tissues was initially predicted via bioinformatics analysis and subsequently confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), which revealed that SNAI2 was highly expressed in glioma tissues as well as GSCs, with an inverse correlation with overall glioma patient survival detected. Loss- and gain- of-function assays were performed to determine the roles of SNAI2 and pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) on GSC viability, proliferation and apoptosis. Data were obtained indicating that SNAI2 promoted the proliferation of GSCs, while overexpressed PHLPP2 brought about a contrasting trend. As detected by chromatin immunoprecipitation, RT-qPCR and agarose gel electrophoresis, SNAI2 bound to the promoter region of PHLPP2 and repressed the transcription of PHLPP2 while SNAI2 was found to inhibit PHLPP2 resulting in activation of the Akt pathway. Finally, the roles of SNAI2 and PHLPP2 were verified in glioma growth in nude mice xenografted with tumor. Taken together, the key findings of the present study suggest that SNAI2 may promote the proliferation of GSCs through activation of the Akt pathway by downregulating PHLPP2.

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“…However, to the best of our knowledge, the role of RAP2C in the regulation of IDD progression has not been previously reported. It has been shown that RAP2C activates ERK signaling ( 13 ), which has been identified as crucial in the modulation of IDD progression ( 14 , 15 ). Pro-inflammatory macrophages promote the degeneration phenotypes of nucleus pulposus (NP) cells partly via JNK and ERK signaling ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑200c‑3p suppresses intervertebral disc degeneration by targeting RAP2C/ERK signaling

et al. 2021

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Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The high morbidity associated with this disease diminishes the quality of life of those who are affected. MicroRNAs (miRs) play crucial roles in various diseases, including IDD. However, the mechanism via which miR-200c-3p plays a role in the development of IDD remains unknown. The present study aimed to investigate the effect of miR-200c-3p on the progression of IDD and the underlying mechanism. The expression level of miR-200c-3p was evaluated in intervertebral disc tissues from patients with IDD. To construct the IDD cell model, the nucleus pulposus (NP) cells were treated with lipopolysaccharide (LPS) 24 h following transfection with miR-200c-3p mimic or inhibitor. A luciferase activity assay was performed, while reverse transcription-quantitative PCR and western blotting were conducted to determine the RNA and protein expression levels, respectively. The expression level of miR-200c-3p in the intervertebral disc tissues of patients with IDD was lower than that of normal subjects. LPS treatment reduced the expression level of miR-200c-3p in NP cells. Moreover, miR-200c-3p mimic inhibited LPS-induced NP cell apoptosis. It was found that miR-200c-3p attenuated inflammatory cytokine levels and extracellular matrix (ECM) degradation in NP cells. Furthermore, miR-200c-3p targeted Ras-related protein 2C (RAP2C) in NP cells. RAP2C promoted apoptosis, inflammatory cytokine levels and ECM degradation by activating ERK signaling. Knockdown of RAP2C and inhibition of ERK signaling by SCH772984 partially reversed the proinflammatory effect of the miR-200c-3p inhibitor on LPS-treated NP cells. Thus, miR-200c-3p inhibits NP cell apoptosis, inflammatory cytokine levels and ECM degradation in IDD by targeting RAP2C/ERK signaling.

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<p>Rap2c as a Novel Biomarker for Predicting Poor Prognosis in Glioma</p>

Cited by 4 publications

References 23 publications

iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy

iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy

Transcription factor SNAI2 exerts pro-tumorigenic effects on glioma stem cells via PHLPP2-mediated Akt pathway

MicroRNA‑200c‑3p suppresses intervertebral disc degeneration by targeting RAP2C/ERK signaling

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