MiR-215, an activator of the CTNNBIP1/ß-catenin pathway, is a marker of poor prognosis in human glioma

Abstract

MicroRNA-215 (miR-215) promotes tumor growth in various human malignancies. However, its role has not yet been determined in human glioma. Here, we found that levels of miR-215 were higher in glioma tissues than in corresponding non-neoplastic brain tissue. High miR-215 expression was correlated with higher World Health Organization (WHO) grades and shorter overall survival. Multivariate and univariate analysis indicated that miR-215 expression was an independent prognostic factor. We also found that TGF-beta1, phosphorylated beta-catenin, alpha-SMA, and fibronectin were increased in glioma tissues. Additionally, CTNNBIP1, a direct target of miR-215, was decreased in glioma compared to adjacent normal tissue. These data indicate that miR-215 activates Wnt/ß-catenin signaling by increasing ß-catenin phosphorylation, a-SMA expression, and fibronectin expression. It promotes TGF-ß1- induced oncogenesis by suppressing CTNNBIP1 in glioma. In summary, miR-215 is overexpressed in human glioma, is involved in TGF-ß1-induced oncogenesis, and can be used as a marker of poor prognosis in glioma patients.