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

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