RNA adenosine modifications related to the prognosis and immune infiltration in osteosarcoma

Background: RNA adenosine modifications, mediated mainly by the “writer” enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognosis role of these genes in osteosarcoma (OS) remains unclear. Methods The univariate and multivariate cox analyses were used to construct the RMWs signature in OS using Target datasets. RMWs expression in OS tissue detected by qPCR analysis. Xcell and GSVA were used for the relationship between RMWs and immune infiltration. DGIdb and CMap databases were used for drug prediction. The vivo and vitro experiments showed that strophanthidin elicited the anti-tumor activity against OS. Results This study constructed the 3-RMWs (CSTF2, ADAR and WTAP) prognosis signature in OS using the Target dataset, and then verified the risk signature using GEO datasets and independent 63 OS tissues using qPCR analysis. The OS patients with high risk observed poor overall survival, and the prognosis signature was the independent prognostic factor in OS. Functional studies showed that tumor-, metabolism-, cell cycle- and immune-related pathways were related high risk. Next, we found that the RMWs- derived high-risk patients showed increased infiltration of Macrophages M2 and cDCs. Furthermore, we predicted the potential drugs for OS using DGIdb and CMap database. The vivo and vitro experiments showed that strophanthidin elicited the anti-tumor activity against OS via repressing cell growth and inducing cell cycle arrest at the G1 phase. Conclusion The 3-RMWs-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS via repressing the growth and cell cycle of OS cells.