Long non-coding RNA DSCAM-AS1 upregulates USP47 expression through sponging miR-101-3p to accelerate osteosarcoma progression

摘要

Osteosarcoma (OS) originating from mesenchyme is one of the most common invasive tumors of bone, and has an extremely high mortality rate. Previous studies have reported that long non-coding RNAs (lncRNAs) play essential roles in the tumorigenesis and progression of a multitude of human cancers. The lncRNA DSCAM-AS1 has been reported to be an oncogenic gene in many cancers. However, the roles and regulatory mechanisms of DSCAM-AS1 in OS have not been deeply investigated. In this study, our findings prove that DSCAM-AS1 is highly expressed in OS cells. Knockdown of DSCAM-AS1 suppressed cell proliferation, migration, and invasiveness, and induced cell apoptosis in OS. Additionally, knockdown of DSCAM-AS1 inactivated the Wnt-beta-catenin signaling pathway. Moreover, research into its molecular mechanisms confirmed that DSCAM-AS1 functions as a sponge for miR-101-3p, and that ubiquitin-specific peptidase 47 (USP47) is a target gene of miR-101-3p. Furthermore, a negative relationship between miR-101-3p and DSCAM-AS1 or USP47 was discovered. The results from our rescue assays suggest that DSCAM-AS1 regulates the progression of OS through binding with miR-101-3p to control the expression of USP47. Finally, we discovered that AKT-mTOR signaling pathway mediates the activity of DSCAM-AS1 in OS. Taken together, our results show that DSCAM-AS1 accelerates the progression of OS via the miR-101-3p-USP47 axis, which could present a new potential therapeutic treatment for OS.