RBPJ contributes to the malignancy of glioblastoma and induction of proneural‐mesenchymal transition via IL‐6‐STAT3 pathway

Zhang, Guangtao; Tanaka, Shingo; Jiapaer, Shabierjiang; Sabit, Hemragul; Tamai, Sho; Kinoshita, Masashi; Nakada, Mitsutoshi

doi:10.1111/cas.14642

Cited by 20 publications

(16 citation statements)

References 51 publications

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“…Mounting evidence indicates that inflammatory factors are found in the tumour microenvironment of many cancers 4 . Pro‐inflammatory factors have been described in glioma, and it is generally considered that IL‐6, IL‐8, CXCL1, CXCL10 and TGFβ2 are pro‐tumour cytokines closely related to glioma progression 5‐9 . Interleukin‐6 (IL‐6) is a cytokine that regulates immune and inflammatory reactions.…”

Section: Introductionmentioning

confidence: 99%

“…4 Pro-inflammatory factors have been described in glioma, and it is generally considered that IL-6, IL-8, CXCL1, CXCL10 and TGFβ2 are protumour cytokines closely related to glioma progression. [5][6][7][8][9] Interleukin-6 (IL-6) is a cytokine that regulates immune and inflammatory reactions. It is expressed in various solid tumours and promotes the invasion and migration of tumour cells.…”

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confidence: 99%

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Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma

Liu

Zhang

et al. 2021

J Cellular Molecular Medi

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Glioblastoma multiforme (GBM), a fatal brain tumour with no available targeted therapies, has a poor prognosis. At present, radiotherapy is one of the main methods to treat glioma, but it leads to an obvious increase in inflammatory factors in the tumour microenvironment, especially IL‐6 and CXCL1, which plays a role in tumour to resistance radiotherapy and tumorigenesis. Casein kinase 1 alpha 1 (CK1α) (encoded on chromosome 5q by Csnk1a1) is considered an attractive target for Tp53 wild‐type acute myeloid leukaemia (AML) treatment. In this study, we evaluated the anti‐tumour effect of Csnk1a1 suppression in GBM cells in vitro and in vivo. We found that down‐regulation of Csnk1a1 or inhibition by D4476, a Csnk1a1 inhibitor, reduced GBM cell proliferation efficiently in both Tp53 wild‐type and Tp53‐mutant GBM cells. On the contrary, overexpression of Csnk1a1 promoted cell proliferation and colony formation. Csnk1a1 inhibition improved the sensitivity to radiotherapy. Furthermore, down‐regulation of Csnk1a1 reduced the production and secretion of pro‐inflammatory factors. In the preclinical GBM model, treatment with D4476 significantly inhibited the increase in pro‐inflammatory factors caused by radiotherapy and improved radiotherapy sensitivity, thus inhibiting tumour growth and prolonging animal survival time. These results suggest targeting Csnk1a1 exert an anti‐tumour role as an inhibitor of inflammatory factors, providing a new strategy for the treatment of glioma.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma

Liu

Zhang

et al. 2021

J Cellular Molecular Medi

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“…In order to verify the function of NPC2 in GBM, we silenced NPC2 in GBM cells. U87-MG and U251 are cell lines often used in the study of GBM ( Gao et al, 2020 ; Tu et al, 2020 ; Xia et al, 2020 ; Zhang G. et al, 2020 ). CCK-8 assay has shown that cell proliferation was inhibited in U87-MG and U251 cells with Sh-NPC2 transfection compared with that in negative control (Sh-NC) ( Figure 6A ).…”

Section: Resultsmentioning

confidence: 99%

NPC2 as a Prognostic Biomarker for Glioblastoma Based on Integrated Bioinformatics Analysis and Cytological Experiments

Shen

Lin

et al. 2021

Front. Genet.

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Glioblastoma (GBM) is one of the most common and fatal malignancies worldwide, while its prognostic biomarkers are still being explored. This study aims to identify potential genes with clinical and prognostic significance by integrating bioinformatics analysis and investigating their function in HNSCC. Based on the Single-cell RNA sequencing (scRNA-seq) results of H3K27M-glioma cells, computational bioinformatics methods were employed for selecting prognostic biomarker for GBM. The protein NPC2 (NPC Intracellular Cholesterol Transporter 2), which has been shown to be related to lipoprotein metabolism and innate immune system, was identified to be upregulated in GBM. NPC2 showed a relatively higher expression in GBM samples, and a negative correlation with tumor purity and tumor infiltrating immune cells. Additionally, NPC2 was knocked down in U87-MG and U251 cells line, and cell proliferation and migration capability were evaluated with CCK-8, scratch and transwell assay, respectively. Cytological experiments has shown that NPC2 overexpression inhibited GBM cells proliferation and migration, indicating its important role in GBM progression. This is the first investigation into the prognostic value of NPC2 interact with GBM. The potential molecular factor NPC2 have been identified as a prognostic biomarker for GBM.

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“…TST is mainly localized to mitochondria and catalyzes the conversion of thiosulfate and cyanide to thiocyanate and sulfite [ 55 ]. As molecular switches in regulating the notch response, transcription factor RBPJ involves in the regulation of the progression of a variety of tumors, such as colorectal cancer [ 56 ], lung cancer [ 57 ], hepatocellular carcinoma [ 58 ], glioblastoma [ 59 , 60 ], and prostate cancer [ 61 ]. As a member of the G protein family, GNA11 plays an important role in tumor progression [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors

Sun

et al. 2022

International Journal of Endocrinology

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Background. Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism. Although numerous studies have studied the subject, the predictive value of gene biomarkers nevertheless remains low. Methods. In this study, we performed genomic analysis of abnormal DNA methylation in parathyroid tumors. After data preprocessing, differentially methylated genes were extracted from patients with parathyroid tumors by using t-tests. Results. After refinement of the basic differential methylation, 28241 unique CpGs (634 genes) were identified to be methylated. The methylated genes were primarily involved in 7 GO terms, and the top 3 terms were associated with cyst morphogenesis, ion transport, and GTPase signal. Following pathway enrichment analyses, a total of 10 significant pathways were enriched; notably, the top 3 pathways were cholinergic synapses, glutamatergic synapses, and oxytocin signaling pathways. Based on PPIN and ego-net analysis, 67 ego genes were found which could completely separate the diseased group from the normal group. The 10 most prominent genes included POLA1, FAM155 B, AMMECR1, THOC2, CCND1, CLDN11, IDS, TST, RBPJ, and GNA11. SVM analysis confirmed that this grouping approach was precise. Conclusions. This research provides useful data to further explore novel genes and pathways as therapeutic targets for parathyroid tumors.

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RBPJ contributes to the malignancy of glioblastoma and induction of proneural‐mesenchymal transition via IL‐6‐STAT3 pathway

Cited by 20 publications

References 51 publications

Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma

Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma

NPC2 as a Prognostic Biomarker for Glioblastoma Based on Integrated Bioinformatics Analysis and Cytological Experiments

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors

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