Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

Xiong, Jing; Zhou, Li; Lim, Yoon Pin; Yang, Miao; Zhu, Yuanyuan; Li, Zhiwei; Fu, Dengli; Zhou, Xin‐Fu

doi:10.3892/ol.2015.3181

Cited by 31 publications

(17 citation statements)

References 25 publications

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“…It has been reported that mature BDNF and its receptor, TrkB, are upregulated in human glioma tissues ( 19 ); however, its specific mechanism of action has not been clearly explained. Thus, the present study also measured the expression of TrkB in the aforementioned cell lines.…”

Section: Resultsmentioning

confidence: 99%

MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells

et al. 2018

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Glioma is the most common type of malignant intracranial tumor in adults and is associated with the highest mortality rate. Although surgery, radiotherapy, chemotherapy and other treatment methods have progressed, the median survival of patients with glioma is only 14–15 months. Glioma cells are able to penetrate along blood vessels and invade into the surrounding normal brain tissue so that an overall resection of the tumor cannot be performed. In the process of metastasis, the resistance of cancer cells to anoikis has an important role. When tumor cells escape from their original environment, anoikis resistance aids their survival. In the present study, reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR), RT-quantitative PCR and western blotting demonstrated that the transcription factor, motor neuron and pancreas homeobox 1 (MNX1), was ectopically expressed in glioma cells compared with normal HUVEC-C human umbilical vein endothelial cells. Furthermore, its expression was higher in more malignant glioma cell lines (T98G and M059K) compared with the less malignant glioma cell line (U-87 MG) and normal HUVEC-C cells. An adhesion assay using fibronectin demonstrated that MNX1 and tyrosine kinase receptor B (TrkB) overexpression in HUVEC-C and U-87 MG cells reduced adhesion and forced them to suspend. Additionally, MNX1 and TrkB overexpression was demonstrated to increase the ability of cells to bypass anoikis. MNX1 and TrkB knockdown increased adhesion and promoted apoptosis after suspension. It was further demonstrated that MNX1 functioned as a transcription factor binding in the upstream regulatory region of TrkB to activate its expression. The results of the present study suggested that MNX1 may suppress the adhesion and apoptosis rates of tumor cells by activating TrkB. The results of the present study suggest that MNX1 may represent a novel therapeutic target for the treatment of gliomas.

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Section: Resultsmentioning

confidence: 99%

MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells

et al. 2018

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“…Interestingly, BDNF-AS was demonstrated to be reversely associated with BDNF and downregulated expressed in RB, NSCLC, and CC 12,39,40 . Xiong et al found that mature BDNF induces glioma cells in vitro 41 . However, little is known about the expression or functions of BDNF-AS in human glioma.…”

Section: Discussionmentioning

confidence: 99%

PABPC1-induced stabilization of BDNF-AS inhibits malignant progression of glioblastoma cells through STAU1-mediated decay

Zheng

et al. 2020

Cell Death Dis

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Glioblastoma is the most common and malignant form of primary central nervous tumor in adults. Long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in modulating gene expression and regulating human tumor's malignant behaviors. In this study, we confirmed that lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) was downregulated in glioblastoma tissues and cells, interacted and stabilized by polyadenylate-binding protein cytoplasmic 1 (PABPC1). Overexpression of BDNF-AS inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of glioblastoma cells. In the in vivo study, PABPC1 overexpression combined with BDNF-AS overexpression produced the smallest tumor and the longest survival. Moreover, BDNF-AS could elicit retina and anterior neural fold homeobox 2 (RAX2) mRNA decay through STAU1-mediated decay (SMD), and thereby regulated the malignant behaviors glioblastoma cells. Knockdown of RAX2 produced tumor-suppressive function in glioblastoma cells and increased the expression of discs large homolog 5 (DLG5), leading to the activation of the Hippo pathway. In general, this study elucidated that the PABPC1-BDNF-AS-RAX2-DLG5 mechanism may contribute to the anticancer potential of glioma cells and may provide potential therapeutic targets for human glioma.

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“…This is emphasized by the negative prognostic effect of VAV3 and NOS2 expression in grade IV astrocytoma and for SPC24 in liver tumours [ 40 ]. Similarly, decreased NTRK2 expression in high compared to low grade astrocytoma [ 41 ], decreased ST3GAL6 expression in liver tumours [ 42 ], and increased AKR1C3 expression in 1q19p co-deleted glioma compared to other glioma subtypes [ 43 ] support a low-malignant function, although other studies on NTRK2 [ 44 , 45 ], AKR1C3 [ 46 , 47 ], and ST3GAL6 [ 48 ] are inconsistent.…”

Section: Discussionmentioning

confidence: 99%

GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile

et al. 2017

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Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas express the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP). Several GFAP splice variants have been identified and the main variants expressed in human astrocytoma are the GFAPα and GFAPδ isoforms. Here we show a significant downregulation of GFAPα in grade IV astrocytoma compared to grade II and III, resulting in an increased GFAPδ/α ratio. Mimicking this increase in GFAPδ/α ratio in astrocytoma cell lines and comparing the subsequent transcriptomic changes with the changes in the patient tumours, we have identified a set of GFAPδ/α ratio-regulated high-malignant and low-malignant genes. These genes are involved in cell proliferation and protein phosphorylation, and their expression correlated with patient survival. We additionally show that changing the ratio of GFAPδ/α, by targeting GFAP expression, affected expression of high-malignant genes. Our data imply that regulating GFAP expression and splicing are novel therapeutic targets that need to be considered as a treatment for astrocytoma.

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Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

Cited by 31 publications

References 25 publications

MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells

MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells

PABPC1-induced stabilization of BDNF-AS inhibits malignant progression of glioblastoma cells through STAU1-mediated decay

GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile

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