Activation of <i>PTGS2</i>/NF‐κB signaling pathway enhances radiation resistance of glioma

Tan, Cheng; Liu, Liang; Liu, Xiaoyang; Qi, Ling; Wang, Weiyao; Zhao, Guifang; Wang, Libo; Dai, Yimeng

doi:10.1002/cam4.1971

Cited by 31 publications

(21 citation statements)

References 29 publications

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“…Increasing evidence has suggested that rapid acquired therapeutic resistance is the major cause of the failure of standard comprehensive treatments, leading to the recurrence and high mortality of glioma . Various molecular pathways have been shown to be responsible for the acquisition of therapeutic resistance in glioma . Therefore, it is essential to identify the mechanisms, especially prognostic biomarkers, underlying therapeutic resistance in glioma.…”

Section: Discussionmentioning

confidence: 99%

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

et al. 2019

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Introduction Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long‐term outcome of glioma. Aims To further investigate prognostic biomarkers and potential therapeutic targets for GBM. Results In this study, we identified tribbles pseudokinase 2 (TRIB2) as one of the genes that is most correlated with pathological classification, radioresistance, and TMZ resistance in glioma. Additionally, the expression of mitogen‐activated protein kinase kinase kinase 1 (MAP3K1) showed a strong correlation with TRIB2. Moreover, a combined increase in TRIB2 and MAP3K1 was observed in GBM and indicated a poor prognosis of patients with glioma. Finally, enriched TRIB2 expression and MAP3K1 expression were shown to be associated with resistance to TMZ and radiotherapy. Conclusion Combined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long‐term outcomes of GBM.

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Section: Discussionmentioning

confidence: 99%

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

et al. 2019

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“…However, the problem with this therapeutic modality is that radiation effects vary dramatically among patients. Moreover, the effects of radiation therapy on radiation resistance are rarely studied [1,2,3,4].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer

Kim

et al. 2019

Cancers

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Despite the importance of radiation therapy, there are few radiation-related markers available for use in clinical practice. A larger catalog of such biomarkers is required to help clinicians decide when radiotherapy should be replaced with a patient-specific treatment. Arachidonate 15-lipoxygenase (15-LOX-1) enzyme is involved in polyunsaturated fatty acid metabolism. When colorectal cancer (CRC) cells were exposed to radiation, 15-LOX-1 was upregulated. To verify whether 15-LOX-1 protects against or induces DNA damage, we irradiated sh15-LOX-1 stable cells. We found that low 15-LOX-1 is correlated with radioresistance in CRC cells. These data suggest that the presence of 15-LOX-1 can be used as a marker for radiation-induced DNA damage. Consistent with this observation, gene-set-enrichment analysis based on microarray experiments showed that UV_RESPONSE was decreased in sh15-LOX-1 cells compared to shCon cells. Moreover, we discovered that the expression of the histone H2A variant macroH2A2 was sevenfold lower in sh15-LOX-1 cells. Overall, our findings present mechanistic evidence that macroH2A2 is transcriptionally regulated by 15-LOX-1 and suppresses the DNA damage response in irradiated cells by delaying H2AX activation.

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“…PTGS2 is one of the rate-limiting enzymes of synthesis of prostaglandins from arachidonic acid. In radiation-resistant glioma cells, PTGS2 expression is up-regulated and increased radio-tolerance by activating downstream signaling effectors NF-κB signaling [ 38 ]. NF-κB signaling is known to maintain the characteristics of CSCs associated with cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and verification of molecular targets in ovarian cancer stem-like cells

Behera

Ashraf

Srivastava

et al. 2020

Heliyon

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Background Epithelial ovarian cancer (EOC) is a lethal and aggressive gynecological malignancy. Despite recent advances, existing therapies are challenged by a high relapse rate, eventually resulting in disease recurrence and chemoresistance. Emerging evidence indicates that a subpopulation of cells known as cancer stem-like cells (CSLCs) exists with non-tumorigenic cancer cells (non-CSCs) within a bulk tumor and is thought to be responsible for tumor recurrence and drug-resistance. Therefore, identifying the molecular drivers for cancer stem cells (CSCs) is critical for the development of novel therapeutic strategies for the treatment of EOC. Methods Two gene datasets were downloaded from the Gene Expression Omnibus (GEO) database based on our search criteria. Differentially expressed genes (DEGs) in both datasets were obtained by the GEO2R web tool. Based on log 2 (fold change) >2, the top thirteen up-regulated genes and log 2 (fold change) < -1.5 top thirteen down-regulated genes were selected, and the association between their expressions and overall survival was analyzed by OncoLnc web tool. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways analysis, and protein-protein interaction (PPI) networks were performed for all the common DEGs found in both datasets. SK-OV-3 cells were cultured in an adherent culture medium and spheroids were generated in suspension culture with CSCs specific medium. RNA from both cell population was extracted to validate the selected DEGs expression by q-PCR. Growth inhibition assay was performed in SK-OV-3 cells after carboplatin treatment. Results A total of 200 DEGs, 117 up-regulated and 83 down-regulated genes were commonly identified in both datasets. Analysis of pathways and enrichment tests indicated that the extracellular matrix part, cell proliferation, tissue development, and molecular function regulation were enriched in CSCs. Biological pathways such as interferon-alpha/beta signaling, molecules associated with elastic fibers, and synthesis of bile acids and bile salts were significantly enriched in CSCs. Among the top 13 up-regulated and down-regulated genes, MMP1 and PPFIBP1 expression were associated with overall survival. Higher expression of ADM, CXCR4, LGR5, and PTGS2 in carboplatin treated SK-OV-3 cells indicate a potential role in drug resistance. Conclusions The molecular signature and signaling pathways enriched in ovarian CSCs were identified by bioinformatics analysis. This analysis could provide further research ideas to find the new mechanism and novel potential therapeutic targets for ovarian CSCs.

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Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma

Cited by 31 publications

References 29 publications

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer

Bioinformatics analysis and verification of molecular targets in ovarian cancer stem-like cells

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