Journal
NEURO-ONCOLOGY
Volume 18, Issue 9, Pages 1288-1296Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/now044
Keywords
glioma; invasion; miR-301a; SEPT7; Wnt/beta-catenin signaling
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Background. miR-301a is frequently dysregulated and specific to human tumors, playing a critical role in tumorigenesis; however, the exact functions and regulatory mechanisms of miR-301a in glioma cells remain largely unknown. Herein, we show that miR-301a activated by the Wnt/beta-catenin pathway promoted the invasion of glioma cells by directly targeting SEPT7. Methods. Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion. Results. Initially, we detected the expression of miR-301a in glioma tissues and identified that miR-301a had increased, with ascending grades of the tumor. Furthermore, high levels of miR-301a were associated with a poorer prognosis in glioma patients. It is important to note that the Wnt/beta-catenin/TCF4 pathway enhanced miR-301a expression by binding to the promoter region. To determine the oncogenic functions of miR-301a in glioma, SEPT7 was supported as the direct target gene. In addition, the Wnt/beta-catenin pathway repressed SEPT7 expression, which was dependent on miR-301a in glioma cells. Finally, miR-301a was activated by Wnt/beta-catenin and then promoted invasion of glioma cells by inhibiting the expression of SEPT7 in vitro and in vivo. Conclusions. Our findings revealed the mechanism of action for miR-301a in tumor cell invasion. Moreover, the Wnt/miR-301a/SEPT7 signaling axis might be a novel target in treating glioma.
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