MiR-301a is activated by the Wnt/β-catenin pathway and promotes glioma cell invasion by suppressing SEPT7.

Abstract

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/β-catenin pathway promoted the invasion of glioma cells by directly targeting SEPT7. Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion. 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/β-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/β-catenin pathway repressed SEPT7 expression, which was dependent on miR-301a in glioma cells. Finally, miR-301a was activated by Wnt/β-catenin and then promoted invasion of glioma cells by inhibiting the expression of SEPT7 in vitro and in vivo. 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.