| OBJECTIVE: Increasing evidences have validated the essential regulation of long non-coding RNAs(Lnc RNAs)in the biological process of tumors.Lnc RNA PXN-AS1 has been discovered to be as a tumor suppressor in pancreatic cancer;however,its function and mechanism remain greatly unknown in glioblastoma(GBM).This study aims to explore the functions and molecular mechanisms of PXN-AS1 implicated in proliferation and chemoresistance in glioma.METHODS: PXN-AS1 expression in glioblastoma cells and paired normal cells were measured by qRT-PCR.The functional roles of PXN-AS1 in glioblastoma were demonstrated by Immunofluorescence staining 、 JC-1 assay 、 western blot,etc.Subcellular fractionation,Chromatin immunoprecipitation,Dual-luciferase reporter gene assay,RNA immunoprecipitation and western blotting were used to demonstrate the potential mechanisms of PXN-AS1.RESULTS: PXN-AS1 was highly expressed in GBM tissues and cells.Besides,the knockdown of PXN-AS1 was closely associated with the inhibitory proliferation and inducing apoptosis of GBM cells.PXN-AS1 inhibition was also found to restrain GBM tumor growth.Importantly,SOX9 functioned as a transcription factor and activated PXN-AS1 expression,and overexpressed PXN-AS1 rescued the inhibitory role of down-regulated SOX9 in GBM cell growth.Subsequently,it was discovered that PXN-AS1 activated Wnt/β-catenin pathway.DKK1 was widely known as an inhibitor gene of Wnt/β-catenin pathway,and its expression was negatively associated with PXN-AS1 and SOX9.Interestingly,we found that PXN-AS1 could recruit EZH2 to mediate the H3K27me3 level of DKK1 promoter.Restoration experiments manifested that DKK1 knockdown counteracted PXN-AS1 depletion-mediated repression in GBM cell growth.CONCLUSION: PXN-AS1 acts as an oncogene in GBM,and SOX9-activated PXN-AS1 promotes GBM progression by epigenetically silencing DKK1,suggesting a helpful revelation for the exploration of novel GBM diagnostic and therapeutic strategies. |
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