Inflammatory landscape of human brain tumors reveals an NFκB dependent cytokine pathway associated with mesenchymal glioblastoma

Zanotto-Filho, Alfeu; Gonçalves, Rosângela Mayer; Klafke, Karina; Souza, Priscila Oliveira de; Dillenburg, Fabiane Cristine; Carro, Luigi; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

doi:10.1016/j.canlet.2016.12.015

Cited by 60 publications

(48 citation statements)

References 56 publications

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“…In addition, CDC25A was reported up-regulated in chondrosarcoma cells and played an important role in cell cycle progression and tumorigenesis of chondrosarcoma as an activator of CDK complexes [50]. Moreover, the activation of PI3K/AKT pathway participated in the glioma progression and various biological effects including proliferation, migration, invasion and apoptosis [51, 52]. The PI3K/AKT pathway inhibitors were discovered to exhibit efficacy against glioblastoma in clinically relevant mouse models [53].…”

Section: Dicussionmentioning

confidence: 99%

RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway

et al. 2017

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BackgroundGlioma is one of the most frequent intracranial malignant tumors. LncRNAs have been identified as new modulators in the origination and progression of glioma.MethodsQuantitative real-time PCR were conducted to evaluate the expression of linc00152 and miRNA-103a-3p in glioma tissues and cells. Western blot were used to determine the expression of FEZF1 and CDC25A in glioma tissues and cells. Stable knockdown of linc00152 or over-expression of miR-103a-3p in glioma stem cells (GSCs) were established to explore the function of linc00152 and miR-103a-3p in GSCs. Further, luciferase reports were used to investigate the correlation between linc00152 and miR-103a-3p. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate the function of linc00152 and miR-103a-3p in GSC malignant biological behaviors. ChIP assays were employed to ascertain the correlations between FEZF1 and CDC25A.ResultsLinc00152 was up-regulated in glioma tissues as well as in GSCs. Knockdown of linc00152 inhibited cell proliferation, migration and invasion, while promoted GSC apoptosis. Linc00152 regulated the malignant behavior of GSCs by binding to miR-103a-3p, which functions as a tumor suppressor. In addition, knockdown of linc00152 down-regulated forebrain embryonic zinc finger protein 1 (FEZF1), a direct target of miR-103a-3p which played an oncogenic role in GSCs. FEZF1 elevated promoter activities and up-regulated expression of the oncogenic gene cell division cycle 25A (CDC25A). CDC25A over-expression activated the PI3K/AKT pathways, which regulated the malignant behavior of GSCs.ConclusionsLinc00152/miR-103a-3p/FEZF1/CDC25A axis plays a novel role in regulating the malignant behavior of GSCs, which may be a new potential therapeutic strategy for glioma therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0677-9) contains supplementary material, which is available to authorized users.

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Section: Dicussionmentioning

confidence: 99%

RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway

et al. 2017

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“…This study showed that bradykinin sequentially increased the phosphorylation of MEK1 and ERK1/2 in human glioblastoma cells. The MEK-ERK signaling pathway was involved in inflammation-associated processes in GBM, including tumor-associated macrophage signatures [29]. Thus, bradykinin-induced activation of MEK1-ERK1/2 directly participates in tumorigenesis of glioblastomas by transducing information from the site of Ca 2+ signal generation in plasma membranes to nuclei.…”

Section: Discussionmentioning

confidence: 99%

The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism

Sun

Chen

Lin

et al. 2020

Cancers

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Glioblastoma multiforme (GBM) is the most common form of brain tumor and is very aggressive. Rapid migration and invasion of glioblastoma cells are two typical features driving malignance of GBM. Bradykinin functionally prompts calcium influx via activation of bradykinin receptor B1/B2 (BDKRB1/2). In this study, we evaluated the roles of bradykinin in migration and invasion of glioblastoma cells and the possible mechanisms. Expressions of aquaporin 4 (AQP4) mRNA and protein were upregulated in human glioblastomas. Furthermore, exposure of human U87 MG glioblastoma cells to bradykinin specifically increased levels of BDKRB1. Successively, bradykinin stimulated influx of calcium, phosphorylation of MEK1 and extracellular signal-regulated kinase (ERK)1/2, translocation and transactivation of nuclear factor-kappaB (NF-κB), and expressions of AQP4 mRNA and protein. Concomitantly, migration and invasion of human glioblastoma cells were elevated by bradykinin. Knocking-down BDKRB1 concurrently decreased AQP4 mRNA expression and cell migration and invasion. The bradykinin-induced effects were further confirmed in murine GL261 glioblastoma cells. Therefore, bradykinin can induce AQP4 expression and subsequent migration and invasion through BDKRB1-mediated calcium influx and subsequent activation of a MEK1-ERK1/2-NF-κB pathway. The bradykinin-BDKRB1 axis and AQP4 could be precise targets for treating GBM patients.

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“…Free NF‐κB is then translocated into the nucleus where it binds to specific DNA sequences called response elements (RE), which leads to recruitment of other proteins such as coactivators and RNA polymerase to promote transcription of downstream target genes . By inducing the transcription of various target genes that regulate cell proliferation, survival, invasion, and angiogenesis, NF‐κB signaling mediates several key biological processes during the development and progression of cancer . However, the processes that lead to abnormal activation of NF‐κB signaling in cancer remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 By inducing the transcription of various target genes that regulate cell proliferation, survival, invasion, and angiogenesis, NF-κB signaling mediates several key biological processes during the development and progression of cancer. [10][11][12] However, the processes that lead to abnormal activation of NF-κB signaling in cancer remain largely unknown. Therefore, it is imperative to study the mechanisms that regulate the NF-κB signaling pathway to identify potential targets for glioma therapy.…”

mentioning

confidence: 99%

Overexpression of SHCBP1 promotes migration and invasion in gliomas by activating the NF‐κB signaling pathway

Zhou

Tan

Chen

et al. 2018

Molecular Carcinogenesis

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Gliomas are common, aggressive central nervous system tumors with poor overall survival rates. Despite improvements in neurosurgery, chemotherapy, and radiotherapy, the outcomes of patients with malignant gliomas remain poor. Therefore, increased knowledge of the molecular mechanisms that regulate glioma progression is crucial to identify novel therapeutic targets. Here, we reported that SHCBP1, a member of Src homolog and collagen homolog (Shc) family, was significantly overexpressed in glioma tissues and glioma cell lines compared to the corresponding normal tissues and cells. Ectopic overexpression of SHCBP1 promoted glioma cell migration and invasion, whereas knockdown of endogenous SHCBP1 had the opposite effects. Importantly, we demonstrated that SHCBP1 promoted aggressiveness in gliomas by activating the NF-κB signaling pathway. Collectively, our study indicates that SHCBP1 plays a pivotal role to promote progression in gliomas and targeting the oncogenic effects of SHCBP1 may provide a clinical strategy to treat gliomas.

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Inflammatory landscape of human brain tumors reveals an NFκB dependent cytokine pathway associated with mesenchymal glioblastoma

Cited by 60 publications

References 56 publications

RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway

RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway

The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism

Overexpression of SHCBP1 promotes migration and invasion in gliomas by activating the NF‐κB signaling pathway

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