Tong Yong-Qing, Liu Bei, Zheng Hong-Yun, Gu Jian, Liu Hang, Li Feng, Tan Bi-Hua, Hartman Melanie, Song Chunhua, Li Yan
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Clinical Molecular Diagnostic Center, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Oncotarget. 2015 Sep 22;6(28):25024-33. doi: 10.18632/oncotarget.4622.
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.
微小RNA-215(miR-215)在多种人类恶性肿瘤中促进肿瘤生长。然而,其在人类胶质瘤中的作用尚未确定。在此,我们发现胶质瘤组织中miR-215的水平高于相应的非肿瘤性脑组织。miR-215高表达与世界卫生组织(WHO)分级较高及总生存期较短相关。多因素和单因素分析表明,miR-215表达是一个独立的预后因素。我们还发现胶质瘤组织中转化生长因子-β1(TGF-beta1)、磷酸化β-连环蛋白、α-平滑肌肌动蛋白(α-SMA)和纤连蛋白增加。此外,与相邻正常组织相比,miR-215的直接靶点CTNNBIP1在胶质瘤中减少。这些数据表明,miR-215通过增加β-连环蛋白磷酸化、α-SMA表达和纤连蛋白表达来激活Wnt/β-连环蛋白信号通路。它通过在胶质瘤中抑制CTNNBIP1促进TGF-β1诱导的肿瘤发生。总之,miR-215在人类胶质瘤中过表达,参与TGF-β1诱导的肿瘤发生,可作为胶质瘤患者预后不良的标志物。