The mir-423-5p/MMP-2 Axis Regulates the Nerve Growth Factor-Induced Promotion of Chondrosarcoma Metastasis

A chondrosarcoma is a common tumor of the soft tissue and bone that has a high propensity to metastasize to distant organs. Nerve growth factor (NGF) is capable of promoting the progression and metastasis of several different types of tumors although the effects of NGF in a chondrosarcoma are not confirmed. Here, we found that the levels of NGF and matrix metalloproteinase-2 (MMP-2) correlated with the tumor stage in patients with a chondrosarcoma. NGF facilitated the MMP-2-dependent cellular migration in human chondrosarcoma JJ012 cells while the overexpression of NGF enhanced the lung metastasis in a mouse model of a chondrosarcoma. NGF promoted the MMP-2 synthesis and cell migration by inhibiting miR-423-5p expression through the FAK and c-Src signaling cascades. NGF appears to be a worthwhile therapeutic target in the treatment of a metastatic chondrosarcoma.

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Nerve growth factor promotes lysyl oxidase-dependent chondrosarcoma cell metastasis by suppressing miR-149-5p synthesis

Cell Death and Disease ◽

10.1038/s41419-021-04392-2 ◽

2021 ◽

Vol 12 (12) ◽

Author(s):

Huey-En Tzeng ◽

Syuan-Ling Lin ◽

Louis Anoop Thadevoos ◽

Ming-Yu Lien ◽

Wei-Hung Yang ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Lysyl Oxidase ◽

Neuronal Cell ◽

Mtor Inhibitors ◽

Tumor Stage ◽

Cellular Migration ◽

Migration And Invasion ◽

Nerve Growth ◽

Human Chondrosarcoma

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.

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

10.21203/rs.3.rs-704561/v1 ◽

2021 ◽

Author(s):

Huey-En Tzeng ◽

Syuan-Ling Lin ◽

Louis Anoop Thadevoos ◽

Ming-Yu Lien ◽

Wei-Hung Yang ◽

...

Keyword(s):

Cell Migration ◽

Nerve Growth Factor ◽

Growth Factor ◽

Lung Metastasis ◽

Lysyl Oxidase ◽

Mtor Signaling ◽

Signaling Cascades ◽

Luciferase Assay ◽

Nerve Growth ◽

Human Chondrosarcoma

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

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