The activation of Toll-like receptor 4 reverses tumor differentiation in human glioma U251 cells via Notch pathway

Hu, Jinyue; Shi, Bizhi; Liu, Xueting; Jiang, Manli; Yuan, Chuang; Jiang, Bimei; Song, Yinghui; Zeng, Yanhua; Wang, Guihua

doi:10.1016/j.intimp.2018.08.019

Cited by 18 publications

(15 citation statements)

References 48 publications

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“…TLR4 activation induces neuronal apoptosis via a TRIF-dependent signaling pathway;33 however, its role in gliomagenesis is ambiguous. On the one hand, Hu et al34 suggested that TLR4 reverses tumor differentiation in human glioma U251 cells that and it could be a biological target for glioma prevention and therapy. On the other hand, TLR4 is significantly decreased in cancer stem cells (CSCs) and suppresses CSC properties by reducing levels of retinoblastoma binding protein 5 35.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p/TLR4 axis

Wu¹,

Hu²,

Costa³

et al. 2019

OTT

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Introduction: Brain glioma is the most common type of primary malignancy in the central nervous system (CNS), with high recurrence and mortality rate, especially glioblastoma (GBM). Recent evidence suggests a role for many long noncoding RNAs (lncRNAs) in the pathogenesis, proliferation, apoptosis, metastasis, and chemotherapeutic resistance of cancer cells. Although the functions of some lncRNAs in the occurrence and development of gliomas have been confirmed, detailed mechanisms of action are lacking. Furthermore, the biological roles of many other lncRNAs in glioma have not been reported at all. Methods: In this study, we identified a novel lncRNA, UBE2R2-AS1, which was dramatically downregulated in glioma compared with normal tissue, by performing microarray detection of six pairs of glioma samples and adjacent normal tissues. In vitro experiments demonstrated that UBE2R2-AS1 regulated glioma cell proliferation, apoptosis, and migration. Results: UBE2R2-AS1 acted as a competing endogenous RNA (ceRNA) to target Toll-like receptor 4 (TLR4) mRNA by binding to miR-877-3p. Furthermore, lncRNA UBE2R2-AS1 suppressed glioblastoma cell growth, migration, and invasion, as well as promoting cell apoptosis by targeting miR-877-3p/TLR4 directly. Conclusion: This information regarding UBE2R2-AS1 and its glioma-related molecular mechanisms will aid the future identification of new lncRNA-directed diagnostics and drug-targeting therapies.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p/TLR4 axis

Wu¹,

Hu²,

Costa³

et al. 2019

OTT

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“…mRNA/protein Tissue Neurons, microglia [13][14][15] mRNA/protein Tissue Astrocytes [16,17] mRNA Cell Lines Glioma (U87, SF126, U251, GI 261) [18] mRNA/protein Tumor/Cell Lines Astrocytoma/GBM (U87MG, A172, LN229, U118) [19] The TLR family is a group of ten receptors (TLR-1-TLR-10) characterized by the detection of a particular pattern of micro-organisms (pathogen-associated molecular patterns (PAMPs)), which are invariable for most pathogens and not present in mammalian organisms. TLR receptors are also sensitive to particles secreted during necrosis and cell death called danger-associated molecular patterns (DAMPs) [20][21][22][23].…”

Section: Tlr-4 Expression Localization Type Of Cellsmentioning

confidence: 99%

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

Litak

Grochowski

Litak³

et al. 2020

IJMS

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Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.

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“…TLR4, the receptor for lipopolysaccharide (LPS), primarily induces inflammatory cytokines in immune cells,28 but it is also involved in carcinogenesis and cancer cell survival. Although TLR4 expression has been reported in a variety of tumors,8,9,11,29 TLR4 expression in patients with PTCL had not been studied. In the present study, we found that high expression of TLR4 was observed in 41.7% of all PTCL patients (60/144), and most frequently in patients with PTCL-NOS (58.8%) and ALK + ALCL (50.0%).…”

Section: Discussionmentioning

confidence: 99%

TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas

Song

Sun

Meng

et al. 2019

CMAR

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Background: Toll-like receptor 4 (TLR4), a member of the pattern recognition receptors, has been reported to be involved in carcinogenesis. However, the clinical impact of TLR4 in peripheral T-cell lymphomas (PTCL) remains unclear. Methods: The current study, using immunohistochemical staining, first examined TLR4 and programmed cell death-ligand 1 (PD-L1) expression in patients with PTCL, to correlate TLR4 and PD-L1 expression with clinicopathological parameters. Results: It was found that the rates of high expression of TLR4 and PD-L1 were 41.7% and 45.8%, respectively. TLR4 expression was closely associated with PD-L1 expression. The expression of TLR4 was closely related to primary extranodal site involvement, increased Ann Arbor stage, and low hemoglobin expression, while the expression of PD-L1 was closely related to a low platelet count and multiple extranodal organ involvements (>1). High expression of either TLR4 or PD-L1 indicated a poor survival rate for patients with PTCL. Multivariate analyses further confirmed that increased expression levels of TLR4 and PD-L1 are unfavorable prognostic factors for PTCL. Conclusion: This study demonstrates that the expressions of TLR4 and PD-L1 are independent predictors of survival time for patients with PTCL. Thus, TLR4 and PD-L1 may serve as potential therapeutic targets in PTCL patients.

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The activation of Toll-like receptor 4 reverses tumor differentiation in human glioma U251 cells via Notch pathway

Cited by 18 publications

References 48 publications

<p>Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p/TLR4 axis</p>

<p>Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p/TLR4 axis</p>

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

<p>TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas</p>

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