RNA-binding Protein NMD3 Promotes Osteosarcoma Cell Proliferation Via Regulating mTOR Signaling Pathway, Exerting Adverse Impacts on Patient Prognosis.

Osteosarcoma (OS) is the most common bone cancer. This study aimed to explore the role of hub RNA binding protein (RBP) in OS, for elucidating its underlying impacts. OS-related public datasets were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Crucial RBP genes were identified integrating differentially expressed analysis, univariate Cox regression analysis, and survival analysis, which were subjected to functional enrichment analysis. The diagnostic and prognostic performance of hub gene was evaluated using receiver operating characteristic (ROC) analysis. The Cell Counting Kit-8 assay, clone formation, wound healing, Transwell assay, and TUNEL assays were performed to explore roles of NMD3 in vitro. High NMD3 expression was significantly associated with poor OS prognosis. Meanwhile, NMD3 showed promising diagnostic and prognostic value in OS. RNA regulation-related pathways, like mTOR signaling pathway, were significantly activated in NMD3-H group. Moreover, differential immune cell infiltration (such as M1 Macrophages) was observed between NMD3-H vs. NMD3-L groups. Furthermore, we found that si-NMD3 significantly inhibited OS cell proliferation and invasion and increased cytokines levels, and OE-NMD3 remarkably activated mTOR signaling pathway in OS cells, via the involvement of ribosome biogenesis. High NMD3 expression activated mTOR signaling pathway, thereby contributed to enhancing OS cell proliferation/ invasion, finally leading to inferior patient outcome.