Background
Glioma is a brain tumor with high morbidity and mortality rates. Understanding its molecular pathogenesis can provide targets and therapeutic strategies for glioma treatment. miR-338-3p represses tumor growth in several cancers, including glioma. Thus, this study aimed to identify the regulatory effects of miR-338-3p/phosphoinositide 3-kinase (PI3K)/Akt/thrombospondins 1 (THBS1) on glioma progression. Materials and
Conclusion
The miR-338-3p/PI3K/Akt/THBS1 regulatory axis can modulate the progression of glioma cell proliferation and migration; thus, it can be considered a therapeutic biomarker. MiR-338-3p is downregulated in glioma.Overregulating miR-338-3p inhibits glioma progression.THBS1 was upregulated in glioma and promotes glioma progression.MiR-338-3p targets THBS1.Overexpressed miR-338-3p targeting THBS1 attenuates glioma progression by PI3K/Akt pathway.
Methods
Quantitative reverse transcription polymerase chain reaction and western blotting were performed to evaluate the levels of miR-338-3p, THBS1, and PI3K/Akt phosphorylation-related proteins. TargetScan software predicted that miR-338-3p targeted THBS1. This was confirmed by performing the dual-luciferase assay. Wound-healing and cell-counting-kit-8 experiments were performed to analyze how THBS1 and miR-338-3p affect the ability of glioma cells to migrate and proliferate. The effect of miR-338-3p on tumorigenicity in mice was also analyzed.
Results
miR-338-3p downregulation was observed in gliomas, whereas THBS1 showed the opposite trend. By suppressing the PI3K/Akt signaling pathway activation, miR-338-3p overregulated the ability of glioma cells to migrate and proliferate in vitro. Additionally, miR-338-3p inhibited the development of glioma tumors in vivo. Moreover, miR-338-3p directly targeted THBS1. THBS1 overexpression promoted glioma cell migration and proliferation by increasing PI3K/Akt phosphorylation. Nonetheless, miR-338-3p overregulation alleviated the effects of THBS1 overexpression.