Identification of pyroptosis-related genes and long non-coding RNAs signatures in osteosarcoma

Zhang, Jian; Deng, Jianjian; Ding, Rui; Yuan, Jinghong; Zhao, Xiaokun; Wu, Tianlong; Jia, Jingyu; Cheng, Xigao

doi:10.1186/s12935-022-02729-1

Cited by 4 publications

(5 citation statements)

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“…Additionally, the overexpression of CHMP4C notably enhanced the proliferation and migration of MG63 cells. Conversely, interference with CHMP4C yielded opposite effects, aligning with the observations reported by Zhang et al (2022). In addition, we validated the in vivo role of CHMP4C.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, we conducted an analysis of CHMP4C and the related proteins GSK3β, p-GSK3β, and β-catenin. CHMP4C is a protein associated with the endocytic pathway and closely linked to processes such as cell division, endocytosis, and signal transduction ( Zhang et al, 2022 ). Research has indicated a significant association between the GSK3β/β-catenin signaling pathway and osteosarcoma proliferation ( Ruan and Zhao, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

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Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation

Jiang,

Zhao,

Zang

et al. 2024

Front. Pharmacol.

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Objective: To investigate the immune mechanism of osteosarcoma (OS)-specific markers to mitigate bone destruction in the aggressive OS, prone to recurrence and metastasis.Methods: Gene expression patterns from the Gene Expression Omnibus (GEO) database (GSE126209) were analyzed using weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, least absolute shrinkage and selection operator (LASSO) modeling, and survival analysis to identify charged multivesicular body protein 4C (CHMP4C). Subsequently, its role in regulating the immune system and immune cell infiltration was explored. CHMP4C expression and signaling molecules in OS were assessed in osteosarcoma cell lines (MG63, U2OS, HOS) and hFOB1.19 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The impact of CHMP4C upregulation and interference on OS-related signaling molecules in MG63 cells was studied. Functional validation of CHMP4C in MG63 OS cells was confirmed through cell counting Kit-8 (CCK-8), transwell, and colony formation assays. In vivo experiments were conducted using Specific Pathogen Free (SPF)-grade male BALB/C nude mice for OS xenograft studies.Results: Based on the gene expression profiles analysis of six osteosarcoma samples and six normal tissue samples, we identified 1,511 upregulated DEGs and 5,678 downregulated DEGs in normal tissue samples. A significant positive correlation between the “yellow-green” module and OS was found through WGCNA analysis. Expression levels of CHMP4C, phosphorylated Glycogen Synthase Kinase 3β (p-GSK3β), and β-catenin were notably higher in U2OS, HOS, and MG63 OS cells than in hFOB1.19 human osteoblasts. Overexpressing CHMP4C in MG63 OS cells upregulated CHMP4C, p-GSK3β, and β-catenin while downregulating GSK3β, leading to increased proliferation and migration of MG63 cells. Conversely, interrupting CHMP4C had the opposite effect. High expression of CHMP4C significantly accelerated the growth of OS in nude mice, resulting in substantial upregulation of CHMP4C, p-GSK3β, and β-catenin expression and suppression of Glycogen Synthase Kinase 3β (GSK3β) expression in OS tissues.Conclusion: CHMP4C may serve as a specific immunomodulatory gene for OS. Its activation of the Wnt/β-catenin signaling pathway, mainly by increasing the phosphorylation echelon of GSK3β, promotes the invasion and spread of OS.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation

Jiang,

Zhao,

Zang

et al. 2024

Front. Pharmacol.

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“…In addition, the AC090559.1 contributes to CASP1, GSDMA expression and thus promotes pyroptosis to inhibit osteosarcoma development. 87 In addition, microRNAs have also been associated with osteosarcoma cell pyroptosis. For example, miRNA‐181a can inhibit NLRP3‐dependent cellular pyroptosis, so low expression of miRNA‐181a contributes to the occurrence of cellular pyroptosis and thus suppresses tumor growth.…”

Section: Mechanisms Of Cell Death In Osteosarcomamentioning

confidence: 99%

“…For example, FOXD2‐AS1 is a proto‐oncogene, which can induce cancer. In addition, the AC090559.1 contributes to CASP1, GSDMA expression and thus promotes pyroptosis to inhibit osteosarcoma development 87 . In addition, microRNAs have also been associated with osteosarcoma cell pyroptosis.…”

Section: Mechanisms Of Cell Death In Osteosarcomamentioning

confidence: 99%

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

Liu,

Wang

et al. 2024

Cancer Medicine

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Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14–19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c‐Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/β‐catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.

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“…Additionally, the role of pyroptosis in osteosarcoma development, although not fully understood, is becoming increasingly recognized, emphasizing the need for further research in this area. 9,10 Pyroptosis is mediated by gasdermin (GSDM) proteins, triggering immune cell activation and infiltration. [11][12][13] The expression of GSDMD, in particular, is essential for the anti-tumour function of CD8 + T cells, 14 and GSDME may act as a tumor suppressor.…”

Section: Introductionmentioning

confidence: 99%

Pyroptosis-Related Gene Signature Predicts Prognosis and Response to Immunotherapy and Medication in Pediatric and Young Adult Osteosarcoma Patients

Guo,

Yang,

2024

JIR

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Purpose Pyroptosis, a new form of inflammatory programmed cell death, has recently gained attention. However, the impact of the expression levels of pyroptosis-related genes (PRGs) on the overall survival (OS) of osteosarcoma patients remains unclear. This study aims to investigate the impact of the expression levels of PRGs on the OS of pediatric and young adult patients with osteosarcoma. Patients and Methods Transcriptome matrix datasets of normal muscle or skeletal tissues from the Genotype-Tissue Expression (GTEx) project and osteosarcoma specimen the National Cancer Institute’s (NCI) Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were used to identify pyroptosis-related genes (PRGs) associated with prognosis. The National Center for Biotechnology Information’s (NCBI) GSE21257 dataset was employed to validate the predictive value of the pyroptosis-related signature (PRS). Additionally, reverse transcription polymerase chain reaction (RT-qPCR) experiment was performed in normal and osteosarcoma cell lines. Results The study identified 18 differentially expressed PRGs (DEPRGs) between normal muscle or skeletal tissues and tumor samples. Multiple machine learning techniques were used to select PRGs, resulting in the identification of four hub PRGs. A PRS-score was calculated for each sample based on the expression of these four hub PRGs, and samples were categorized into low and high PRS-score level groups. It was confirmed that metastatic status and PRS-score level are independent prognostic predictors. A nomogram model for predicting OS of osteosarcoma patients was constructed. Single-cell RNA-sequencing data display the expression patterns of the hub PRGs. RT-qPCR data results were found to be consistent with the differential expression analysis performed on TARGET and GTEx samples. Conclusion The study developed a novel pyroptosis-related gene signature that can stratify pediatric and young adult osteosarcoma patients into different risk groups, thus predicting their response to immunotherapy and chemotherapy.

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Identification of pyroptosis-related genes and long non-coding RNAs signatures in osteosarcoma

Cited by 4 publications

References 66 publications

Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation

Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

Pyroptosis-Related Gene Signature Predicts Prognosis and Response to Immunotherapy and Medication in Pediatric and Young Adult Osteosarcoma Patients

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