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Objective: Dysregulated lipid metabolism enhances the development and advancement of many cancers, including osteosarcoma (OS); however, the underlying mechanisms are still largely unknown. Therefore, this investigation aimed to elucidate novel potential lipid metabolism-related long non-coding RNAs (lncRNAs) that regulate OS development and provide novel signatures for its prognosis and precise treatment. Materials and methods: The GEO datasets (GSE12865 and GSE16091) were downloaded and analyzed using R software packages. Immunohistochemistry (IHC) was used to evaluate protein levels in OS tissues while real-time qPCR was used to measure lncRNA levels, and MTT assays were used to assess OS cell viability. Results: Two lipid metabolism-associated lncRNAs (LM-lncRNAs), small nucleolar RNA host gene 17 (SNHG17) and LINC00837, were identified as efficient and independent prognostic indicators for OS. In addition, further experiments confirmed that SNHG17 and LINC00837 were significantly elevated in OS tissues and cells than para-cancerous counterparts. Knockdown of SNHG17 and LINC00837 synergistically suppressed the viability of OS cells, whereas overexpression of the two lncRNAs promoted OS cell proliferation. Moreover, bioinformatics analysis was conducted to construct six novel SNHG17-microRNA-mRNA competing endogenous RNA (ceRNA) networks, and three lipid metabolism-associated genes (MIF, VDAC2, and CSNK2A2) were found to be abnormally upregulated in OS tissues, suggesting that they were potential effector genes of SNHG17. Conclusion: In summary, SNHG17 and LINC00837 were found to promote OS cell malignancy, suggesting their use as ideal biomarkers for OS prognosis and treatment. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common chronic joint degenerative disease and a major cause of disability in the elderly. However, the current intervention strategies cannot effectively improve OA, and the pathogenesis of OA remains elusive. The present study identified RNA binding motif protein 47 (RBM47) as an upstream modulator of key dysregulation gene co-expression module based on weighted gene co-expression network analysis (WGCNA) analysis and least absolute shrinkage and selection operator (Lasso) modeling. Subsequently, data from real-time quantitative PCR and western blot analysis revealed that RBM47 was upregulated in OA models in vivo and in vitro compared with normal controls. Functional analysis results from the MTT assay, flow cytometry, evaluation of LDH activities and inflammatory mediators, and western blot analysis of extracellular matrix (ECM) proteins, showed that RBM47 knockdown significantly alleviated inflammation, apoptosis, and ECM degradation in interleukin 1β (IL-1β)-treated chondrocytes. Mechanistically, RBM47 bound to F box only protein 2 (FBXO2) and stabilized FBXO2 messenger RNA (mRNA) to promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in chondrocytes. Results from the recovery assay showed that the re-activation of STAT3 signaling by overexpressing FBXO2 or STAT3 counteracted the alleviating effect of RBM47 downregulation on IL-1β-induced inflammation, apoptosis, and ECM degradation. Altogether, our findings illustrate that RBM47 stabilizes FBXO2 mRNA to advance OA development by activating STAT3 signaling, which enhances our understanding of the molecular regulatory mechanisms underlying the development of OA. [ABSTRACT FROM AUTHOR]