Long non-coding RNA DUXAP10 exerts oncogenic properties in osteosarcoma by recruiting HuR to enhance SOX18 mRNA stability

Abstract

AbstractRecent studies have demonstrated that several long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of osteosarcoma (OS). However, more lncRNAs and their mechanisms in regulating growth and migration of OS cells remain to be investigated. In this study, we identified an lncRNA called DUXAP10 by analysis of GEO data, which was significantly up-regulated in OS tissues and cell lines. Experiments in vitro revealed that lncRNA DUXAP10 promoted proliferation, migration, and invasion of OS cells and inhibited their apoptosis. We also demonstrated that DUXAP10 promoted the formation and growth of OS by tumor formation assay. Furthermore, SOX18 was identified as a critical downstream target of DUXAP10 by transcriptome RNA-seq. Mechanistically, DUXAP10 mainly localized in cytoplasm and could specifically bind to HuR to increase the stability of SOX18 mRNA. Meanwhile, SOX18 knockdown largely reversed increased proliferation of OS cells induced by DUXAP10 overexpression. Findings from this study indicate that lncRNA DUXAP10 can act as an oncogene in osteosarcoma by binding HuR to up-regulate the expression of SOX18 at a post-transcriptional level, which may provide a new target for OS clinical diagnosis and treatment.