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

Yong-Qing Tong,Hong-Yun Zheng,Jian Gu,Feng Li,Hang Liu,Melanie Hartman,Bi-Hua Tan,Bei Liu,Chunhua Song,Yan Li

doi:10.18632/oncotarget.4622

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/β-catenin signaling by increasing β-catenin phosphorylation, α-SMA expression, and fibronectin expression. It promotes TGF-β1-induced oncogenesis by suppressing CTNNBIP1 in glioma. In summary, miR-215 is overexpressed in human glioma, is involved in TGF-β1-induced oncogenesis, and can be used as a marker of poor prognosis in glioma patients.

Highlights

Gliomas account for over 50% of brain tumors and are the most serious form of central nervous system tumors that affect adults [1]
To explore the effect of miRNAs on human gliomas, we measured the expression of miRNAs in human glioma tissue and found that miR-215 is the most highly expressed. miR-372, miR-21, mIR10b, and miR-17 were intermediately expressed, and 10 other miRNAs were expressed at a lower level (Fig. 1)
We further examined miR-215 expression in 179 primary glioma and 20 non-neoplastic brain tissues by quantitative real-time PCR

Summary

Introduction

Gliomas account for over 50% of brain tumors and are the most serious form of central nervous system tumors that affect adults [1]. The most common grading system for gliomas is the World Health Organization (WHO) classification of 2007, under which tumors are graded from I (least advanced disease / best prognosis) to IV (most advanced disease / worst prognosis) [2]. Gliomas originate from astrocytes, oligodendrocytes, or ependymal cells with tumors usually displaying a mixture of two or three of these different glial cell types. Glioblastoma multiforme (GBM) is the most lethal primary malignancy of the central nervous system (CNS) because it is extremely aggressive [3]. Most gliomas are highly malignant with a poor prognosis [4]

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Results

Conclusion