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

2015; Impact Journals LLC; Volume: 6; Issue: 28 Linguagem: Inglês

10.18632/oncotarget.4622

1949-2553

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

Circular RNAs in diseases

// Yong-Qing Tong 1, 2 , Bei Liu 3 , Hong-Yun Zheng 2 , Jian Gu 1 , Hang Liu 2 , Feng Li 1 , Bi-Hua Tan 4 , Melanie Hartman 4 , Chunhua Song 4 , Yan Li 1, 2 1 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, PR China 2 Clinical Molecular Diagnostic Center, Renmin Hospital of Wuhan University, Wuhan 430060, PR China 3 Department of Pathology Affiliated Tianyou Hospital of Wuhan University of Science and Technology, Wuhan 430064, PR China 4 Pennsylvania State University College of Medicine and Hershey Medical Center, Hershey, Pennsylvania 17033, USA Correspondence to: Yan Li, e-mail: yanlitf@gmail.com Chunhua Song, e-mail: csong@hmc.psu.edu Keywords: miR-215, glioma, prognosis, CTNNBIP1, TGF-β1 Received: April 19, 2015 Accepted: July 08, 2015 Published: July 22, 2015 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.