MicroRNA (miR)-mediated mRNA and multiple signaling pathway dysregulations have been extensively implicated in several cancer types, including gliomas. Although previous studies have reported that miR-301a acts as an oncogene, the underlying mechanisms of miR-301a in the initiation and progression of glioma remain unknown. The present study aimed to investigate the involvement of miR-301a-mediated signaling pathway dysregulation in glioma. The results identified that miR-301a was significantly upregulated in gliomas and was associated with a poor prognosis based on The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Moreover, zinc and ring finger 3 (ZNRF3) exerted a critical role in the miR-301a-mediated effects on the malignant phenotype, such as by affecting proliferation and apoptosis. Mechanistically, the TOP/FOP luciferase assay, western blotting and immunofluorescence results demonstrated that miR-301a knockdown inhibited the wnt/β-catenin signaling pathway, at least partially via ZNRF3, while ZNRF3 was a direct functional target of miR-301a, as indicated by luciferase reporter assay and western blot analysis. Furthermore, ZNRF3 could in turn repress miR-301a expression, which was dependent on the wnt pathway. Collectively, the present study identified a novel miR-301a/ZNRF3/wnt/β-catenin signaling feedback loop that serves critical roles in glioma tumorigenesis, and that may represent a potential therapeutic target.
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