scholarly journals Nerve Growth Factor Promotes Lysyl Oxidase-dependent Chondrosarcoma Cell Metastasis by Suppressing miR-149-5p Synthesis

Author(s):  
Huey-En Tzeng ◽  
Syuan-Ling Lin ◽  
Louis Anoop Thadevoos ◽  
Ming-Yu Lien ◽  
Wei-Hung Yang ◽  
...  

Abstract Background: The effects of Nerve growth factor (NGF) in chondrosarcoma are not confirmed, although NGF is capable of promoting the progression and metastasis of several different types of tumors. Here we aim to explore the role of NGF in chondrosarcoma and elucidate how NGF acts.Methods: Immunohistochemistry (IHC)-stained tissue samples from chondrosarcoma patients were stained with NGF and LOX antibodies. Cell migration was examined by Transwell migration and invasion assays. The expression levels of LOX, microRNA-149-5p (miR-149-5p) were measured by quantitative real-time polymerase chain reaction. LOX, PI3K, Akt, and mTOR protein expression were examined by Western blot assays. The interaction between LOX 3’-UTRs and miR-149-5p binding site was explored by luciferase assay. We established the orthotopic in vivo model of chondrosarcoma lung metastasis to further investigate the promoting effects of NGF in metastatic chondrosarcoma. Results: Here, we found that the levels of NGF and lysyl oxidase (LOX) correlated with tumor stage in patients with chondrosarcoma. NGF facilitated LOX-dependent cellular migration in human chondrosarcoma JJ012 cells, while overexpression of NGF enhanced lung metastasis in a mouse model of chondrosarcoma. NGF promoted LOX synthesis and cell migration by inhibiting miR-149-5p expression through the PI3K, Akt and mTOR signaling cascades. NGF appears to be a worthwhile therapeutic target in the treatment of metastatic chondrosarcoma.Conclusions: Our study has identified that NGF promotes LOX-dependent cell migration in human chondrosarcoma tissue by inhibiting miR-149-5p synthesis via the PI3K, Akt and mTOR signaling cascades

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Huey-En Tzeng ◽  
Syuan-Ling Lin ◽  
Louis Anoop Thadevoos ◽  
Ming-Yu Lien ◽  
Wei-Hung Yang ◽  
...  

AbstractChondrosarcoma is a malignancy of soft tissue and bone that has a high propensity to metastasize to distant organs. Nerve growth factor (NGF) is critical for neuronal cell growth, apoptosis, and differentiation, and also appears to promote the progression and metastasis of several different types of tumors, although the effects of NGF upon chondrosarcoma mechanisms are not very clear. We report that NGF facilitates lysyl oxidase (LOX)-dependent cellular migration and invasion in human chondrosarcoma cells, and that NGF overexpression enhances lung metastasis in a mouse model of chondrosarcoma. NGF-induced stimulation of LOX production and cell motility occurs through the inhibition of miR-149-5p expression, which was reversed by PI3K, Akt, and mTOR inhibitors and their respective short interfering RNAs. Notably, levels of NGF and LOX expression correlated with tumor stage in human chondrosarcoma samples. Thus, NGF appears to be a worthwhile therapeutic target for metastatic chondrosarcoma.


Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
K Seidler ◽  
A Sydykov ◽  
S Müller-Brüsselbach ◽  
R Müller ◽  
N Weißmann ◽  
...  

2021 ◽  
Vol 19 (12) ◽  
pp. 2529-2536
Author(s):  
Naitian Wang ◽  
Duohui Liu ◽  
Xinyu Ning ◽  
Zhanjun Li ◽  
Lan Dong

Purpose: Sevoflurane is the most commonly used anesthetic agent for surgery. However, it is associated with deficiency in learning and memory abilities. The study was aimed at investigating the role of nerve growth factor (NGF) in sevoflurane anesthesia-induced nerve injury.Methods: RT-qPCR assay was applied to measure expressions of NGF, miR-98-5p and other factors related to apoptosis. CCK-8 assay was used for detecting cell viability while luciferase reporter assay was employed to measure binding condition between miR-98-5p and NGF. Expressions of proteins in PI3K/AKT/mTOR signaling pathway was measured with western blot.Results: Sevoflurane reduced cell viability of RGC-5 cells, promoted apoptosis and reduced the expression of NGF. In sevoflurane-induced RGC-5 cells, over-expression of NGF promoted cell viability with reduced apoptosis. Also, there was reduction in the protein expression of PI3K/AKT/mTOR signaling pathway by sevoflurane, while up-regulation of NGF promoted the expressions of these proteins. In the presence of PI3K inhibitor, reduction cell viability was reduced but apoptosis increased. Luciferase reporter assay detected MiR-98-5p as the target gene of NGF and its overexpression restored high cell viability in the over-expressed NGF. The rate of apoptosis and expressions of proteins was also restored with up-regulation of miR-98-5p.Conclusion: Sevoflurane caused damage to nerve cells, while over-expression of NGF reduced the injury through PI3K/AKT/mTOR signaling pathway and suppression of miR-98-5p. Keywords: Nerve growth factor, Sevoflurane, Nerve injury, Anesthesia, miR-98-5p


2014 ◽  
Vol 9 (6) ◽  
pp. 602 ◽  
Author(s):  
Yixia Yin ◽  
Fang Liu ◽  
Haiwei Zhang ◽  
Kaiming Zhang ◽  
Xinyu Wang ◽  
...  

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Wesley Kephart ◽  
Christopher Mobley ◽  
Carlton Fox ◽  
Vincent Santucci ◽  
Trent Wilson ◽  
...  

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