Wang Kun, Xie Dajiang, Xie Jixi, Wan Yingfeng, Ma Li, Qi Xuchen, Yang Shuxu
Department of Neurosurgery, Sir Run Run Shaw Hospital, College of Medical Sciences, Zhejiang University, Hangzhou, China.
Neuroreport. 2015 Aug 19;26(12):695-702. doi: 10.1097/WNR.0000000000000410.
Glioma is one of the most common intracranial tumors, and the prognosis is poor, although more and more treatments are employed. Wnt/beta-catenin signaling has been reported to be associated with glioma. SFRP1 acts as an antagonist and inhibits Wnt signaling by binding to Wnt molecules. In the present study, we aimed to investigate miRNA-27a as an antineoplastic factor that inhibits the Wnt/beta-catenin pathway by binding to the SFRP1 3'-UTR in glioma in vitro. We first showed that the expression of miR-27a was elevated in both glioma samples and cell lines. Furthermore, downregulation of miR-27a induced growth inhibition, cycle arrest, and apoptosis, and suppressed invasion/migration in glioma cell lines. Quantitative real-time PCR, western blot, and luciferase assay analysis showed that SFRP1 is a direct target of miR-27a. Overexpression of SFRP1 inhibited the malignancy of glioma cell lines. Our investigation showed that downregulation of miR-27a suppressed beta-catenin/TCF-4 transcription activity by targeting SFRP1. Our findings identify a role for miR-27a in glioma cell viability, cycle, apoptosis, and invasion/migration after activation of Wnt/beta-catenin signaling through SFRP1.
胶质瘤是最常见的颅内肿瘤之一，尽管采用了越来越多的治疗方法，但其预后仍然很差。据报道，Wnt/β-连环蛋白信号通路与胶质瘤有关。分泌型卷曲相关蛋白1（SFRP1）作为拮抗剂，通过与Wnt分子结合来抑制Wnt信号通路。在本研究中，我们旨在探讨miRNA-27a作为一种抗肿瘤因子，在体外通过与胶质瘤中的SFRP1 3'-非翻译区（3'-UTR）结合来抑制Wnt/β-连环蛋白通路。我们首先发现，miR-27a在胶质瘤样本和细胞系中的表达均升高。此外，miR-27a的下调诱导了胶质瘤细胞系的生长抑制、细胞周期停滞和凋亡，并抑制了其侵袭/迁移。定量实时聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法（western blot）和荧光素酶报告基因检测分析表明，SFRP1是miR-27a的直接靶点。SFRP1的过表达抑制了胶质瘤细胞系的恶性程度。我们的研究表明，miR-27a的下调通过靶向SFRP1抑制了β-连环蛋白/TCF-4转录活性。我们的研究结果确定了miR-27a在通过SFRP1激活Wnt/β-连环蛋白信号通路后，在胶质瘤细胞活力、细胞周期、凋亡以及侵袭/迁移中所起的作用。
