GAS5 Attenuates Malignant Progression of Glioma Stem-like Cells via Regulating E-cadherin

Background: It is commonly understood that glioma stem-like cells (GSCs) play a vital role in the malignant progression of glioma. Recent studies have reported that long non-coding RNAs (lncRNAs) closely associate with glioma development, however, the underlying molecular regulatory mechanisms on GSCs have not been fully clarified. Methods: LncRNA GAS5 expression level was analyzed by bioinformatics and qRT-PCR assays. GSCs were separated from glioma tissues and identified using immunofluorescence and flow cytometry. Cell proliferation ability was measured by EdU assays. Cell invasion and migration ability was evaluated by transwell assays. Cell apoptosis was measured by flow cytometry. Subcutaneous tumorigenesis assays were performed to explore the GSCs growth in vivo. Luciferase reporter assays were used to identify the direct molecular interaction. E-cadherin expression level was measured by qRT-PCR assays and western blot. Results: In this study, we established two highly malignant glioma stem-like cells from clinical surgical specimens, and found that lncRNA GAS5 was downregulated in GSCs and high-grade glioma tissues, and showed a correlation with patient survival. Functional assays showed that depleting GAS5 promoted the proliferation, invasion, migration, stemness and tumorigenicity, and inhibited apoptosis of GSCs. Mechanistically, GAS5 directly sponge with miR-23a which acts as an oncogene by regulating E-cadherin (CDH1). In addition, rescue experiments demonstrated that GAS5 modulate both the expression and function of E-cadherin via the dependent manner of miR-23a. Conclusions: GAS5 functions as a suppressor in GSCs by targeting the miR-23a/CDH1 axis, which may be a promising therapeutic target against gliomas.