LncRNA GAS5 Inhibits Temozolomide Chemoresistance to Glioma Via Inactivating Wnt/β-Catenin Pathway by Interacting with PTBP1

Abstract

Purpose Temozolomide-based therapeutic resistance has become the crucial cause of chemotherapy failure in glioma treatment. Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) is reported to be downregulated in glioma and to inhibit tumor progression and metastasis. This study aimed to investigate function and potential regulatory mechanism of GAS5 in temozolomide (TMZ) chemoresistance to glioma.Methods qRT-PCR, western blotting and immunofluorescence were used to measure the levels of GAS5 and proteins. RNA-binding protein immunoprecipitation assay was used to analyze the interaction between GAS5 and PTBP1. Flow cytometry apoptosis assay, CCK-8 assay, colony formation assay and nude mice xenograft experiments were used to detect the effects of GAS5 on TMZ resistance in glioma.Results Downregulation of GAS5 might predict a poor prognosis in glioma patients. Overexpression of GAS5 improves the sensitivity to TMZ in glioma cells. Mechanistically, GAS5 could interact with polypyrimidine tract binding protein 1 (PTBP1) to downregulate its expression, thereby inactivating the Wnt/β-catenin pathway. Moreover, GAS5 could increase the anti-tumor effect of TMZ in vivo. Conclusion This study indicated that GAS5 contributed to TMZ chemoresistance of glioma through interacting with PTBP1, and then inhibiting Wnt/β-catenin pathway, which provides a novel approach to develop promising therapeutic strategy.