The hsa_circ_0024183 may affects glioblastoma progression by interacting with the protooncogene SALL4

Abstract

Purpose: The pathogenesis of glioma is not clear, SALL4 is a protooncogene and has been shown to promote the growth of glioma cells. CircRNAs have been shown to play a role in the development of tumors, but the relationship between SALL4 and circRNAs has not been well characterized. The aim of this study is to establish the association between SALL4 and circRNAs.Methods: The circRNAs and miRNAs related to SALL4 screened before were detected in glioma and normal brain tissue samples, then hsa_circ_0024183 was selected to determine its effect on glioma progression in vivo and vitro. The interaction between hsa_circ_0024183, miR-485-5p and SALL4 was clarified by double luciferase assay and RNA immunoprecipitation analysis.Results: The expression of hsa_circ_0024183 was significantly higher in glioma patients and human glioblastoma cell lines than in normal brain(P<0.05). GBM patients with higher hsa_circ_0024183 expression had worse outcome. The reduction of hsa_circ_0024183 by siRNA was found to decrease the proliferation, migration, and invasion abilities of GBM cells and block their cell cycles at the S phase. Furthermore, a decrease of hsa_circ_0024183 expression in GBM cells was found to inhibit their tumorigenicity in nude mice. Mechanistic studies revealed that hsa_circ_0024183 can regulate SALL4 expression by sponging miR-485-5p. And hsa_circ_0024183 RNA could directly bind to SALL4 protein.Conclusion: Interference with hsa_circ_0024183 can reduce the expression of SALL4 and the binding of hsa_circ_0024183 to SALL4 protein. It may affect the progression of glioma through the PTEN/PI3K/Akt pathway. This discovery provides an opportunity to develop potential targeted therapy against glioma.