BDNF: An Oncogene or Tumor Suppressor?

Radin, Daniel P.; Patel, Parth R.

doi:10.21873/anticanres.11783

Cited by 42 publications

(47 citation statements)

References 42 publications

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“…12 BDNF, a member of the neurotrophin family, has been shown to be involved in the initiation and development of various cancers. 30 We investigated the associated mechanism involving circHIPK3, miR-107 and BDNF in GC cells by Western blot. Our data indicated that circHIPK3 regulates the proliferation and migration of GC cells via the miR-107/BDNF axis.…”

Section: Discussionmentioning

confidence: 99%

<p>circHIPK3 Promotes Cell Proliferation and Migration of Gastric Cancer by Sponging miR-107 and Regulating BDNF Expression</p>

Wei¹,

Xu²,

Wei³

et al. 2020

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Background: Circular RNAs (circRNAs) play important regulatory roles in cancer development. However, the mechanisms by which circRNAs regulate gene expression in gastric cancer (GC) remain unclear. Methods: Human GC samples and their matched normal adjacent tissues were obtained from 30 patients to assess the expression of circHIPK3 and its relationship with GC proliferation and migration. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circHIPK3 in GC proliferation and migration, and its underlying molecular mechanisms. Results: Using a circRNA microarray we found a circRNA termed circHIPK3 that performed a significant regulatory role in GC. circHIPK3 was further confirmed to be upregulated in all GC tissues and cells tested. Furthermore, circHIPK3 levels were associated with Tumor & Lymph Node & Metastasis(TNM) stage (P = 0.032). The area under the receiver operating characteristic curve (ROC) was 0.743 (95% confidence interval 0.615-0.872; P = 0.001). CCK-8, colony formation, Transwell and EdU assays were performed to evaluate the effects of circHIPK3 on cell proliferation and migration in GC. Moreover, circHIPK3 was identified as a sponge of miR-107, and as such it regulated brain-derived neurotrophic factor (BDNF), which plays a pivotal role in the development of GC. Conclusion: circHIPK3 represents a novel potential biomarker and therapeutic target of GC.

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Section: Discussionmentioning

confidence: 99%

<p>circHIPK3 Promotes Cell Proliferation and Migration of Gastric Cancer by Sponging miR-107 and Regulating BDNF Expression</p>

Wei¹,

Xu²,

Wei³

et al. 2020

OTT

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“…The direct oncogenic activity of TrkB might also be due to the crosstalk with EGF receptors that together with its ligand is well-known to promote cell transformation. BDNF administration not only does phosphorylate TrkB but also EGFR [ 257 ]. In line with these observations, it has been recently shown that BDNF produced by glioblastoma (GBM) differentiated cells acts on GBM stem cells, fostering their growth through paracrine signaling [ 258 ].…”

Section: Bdnf and Brain Cancer: An Unexpected Role An Oncogene Ormentioning

confidence: 99%

Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

Colucci-D’Amato

Speranza

Volpicelli

2020

IJMS

455

249

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Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal differentiation, it influences serotonergic and dopaminergic neurotransmission. BDNF acts as paracrine and autocrine factor, on both pre-synaptic and post-synaptic target sites. It is crucial in the transformation of synaptic activity into long-term synaptic memories. BDNF is considered an instructive mediator of functional and structural plasticity in the central nervous system (CNS), influencing dendritic spines and, at least in the hippocampus, the adult neurogenesis. Changes in the rate of adult neurogenesis and in spine density can influence several forms of learning and memory and can contribute to depression-like behaviors. The possible roles of BDNF in neuronal plasticity highlighted in this review focus on the effect of antidepressant therapies on BDNF-mediated plasticity. Moreover, we will review data that illustrate the role of BDNF as a potent protective factor that is able to confer protection against neurodegeneration, in particular in Alzheimer’s disease. Finally, we will give evidence of how the involvement of BDNF in the pathogenesis of brain glioblastoma has emerged, thus opening new avenues for the treatment of this deadly cancer.

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“…Consequently, BDNF crucially regulates learning and memory processes in young and adult mammals (see, e.g., Boschen and Klintsova 2017;Gomez-Pinilla and Vaynman 2005) such that imbalances in BDNF levels and downstream signaling via its cognate TrkB tyrosine kinase receptor are associated with neurodegenerative and psychiatric diseases, like Alzheimer's disease, major depressive disorder (Castren and Hen 2013), or schizophrenia (Mohammadi et al 2018). Moreover, BDNF signaling also contributes to physiological functions of the heart and the vasculature and is involved in disorders like coronary artery disease (Ejiri et al 2005;Jin et al 2018;Kaess et al 2015), diabetes mellitus (Eyileten et al 2017;Suwa et al 2006), inflammatory diseases such as asthma (Prakash and Martin 2014), different types of cancer (Chopin et al 2016;Radin and Patel 2017), as well as pain sensation (Deitos et al 2015;Haas et al 2010;Laske et al 2007;Merighi et al 2008;Sapio et al 2019). Furthermore, BDNF levels in preterm neonates differ from BDNF levels in full-term neonates (Malamitsi-Puchner et al 2004), thereby affecting cognitive development in early postnatal life (Chau et al 2017) and potentially being associated with children's mental diseases such as autism spectrum disorders (Qin et al 2016;Zheng et al 2016).…”

Section: Bdnf In Health and Diseasementioning

confidence: 99%

The physiology of regulated BDNF release

2020

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The neurotrophic factor BDNF is an important regulator for the development of brain circuits, for synaptic and neuronal network plasticity, as well as for neuroregeneration and neuroprotection. Up- and downregulations of BDNF levels in human blood and tissue are associated with, e.g., neurodegenerative, neurological, or even cardiovascular diseases. The changes in BDNF concentration are caused by altered dynamics in BDNF expression and release. To understand the relevance of major variations of BDNF levels, detailed knowledge regarding physiological and pathophysiological stimuli affecting intra- and extracellular BDNF concentration is important. Most work addressing the molecular and cellular regulation of BDNF expression and release have been performed in neuronal preparations. Therefore, this review will summarize the stimuli inducing release of BDNF, as well as molecular mechanisms regulating the efficacy of BDNF release, with a focus on cells originating from the brain. Further, we will discuss the current knowledge about the distinct stimuli eliciting regulated release of BDNF under physiological conditions.

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BDNF: An Oncogene or Tumor Suppressor?

Cited by 42 publications

References 42 publications

<p>circHIPK3 Promotes Cell Proliferation and Migration of Gastric Cancer by Sponging miR-107 and Regulating BDNF Expression</p>

<p>circHIPK3 Promotes Cell Proliferation and Migration of Gastric Cancer by Sponging miR-107 and Regulating BDNF Expression</p>

Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

The physiology of regulated BDNF release

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