microRNA profiles of meningiomas

Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, usually benign and frequently associated with neurofibromatosis type 2. Here we define a human meningioma-typical miRNA profile and characterize effects of one down-regulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Up-regulation of miR-200a decreased expression of transcription factors, ZEB1 and SIP1, with consequently increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Down-regulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of β -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target β -catenin mRNA, thereby inhibiting its translation and blocking β -catenin-Wnt signaling, frequently involved in cancer. A direct correlation was found between down-regulation of miR-200a and up-regulation of β-catenin in human meningioma samples. Thus, miR-200a appears to act as a multi-functional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and β -catenin-Wnt signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas. 14 meningioma tumor samples were compared to 3 arachnoidal tissue control samples. Two technical replicates were performed for each sample. Normalization and processing included combining the data from technical replicates. The below table contains quantile-normalized data.

脑膜瘤（Meningiomas）是人类最常见的颅内肿瘤之一，起源于与脑脑膜（brain meninges）相关的蛛网膜细胞（arachnoidal cells），大多为良性病变，且常与2型神经纤维瘤病（neurofibromatosis type 2）相关。本研究明确了人脑膜瘤典型的微小核糖核酸（microRNA, miRNA）表达谱，并表征了一条下调的微小核糖核酸miR-200a对肿瘤生长的调控作用。上调miR-200a的表达可在体外培养体系及体内肿瘤模型中抑制脑膜瘤细胞的增殖。上调miR-200a的表达可降低转录因子ZEB1与SIP1的表达水平，进而上调与细胞分化相关的黏附蛋白E-钙粘蛋白（E-cadherin）的表达。在脑膜瘤及蛛网膜细胞中下调miR-200a的表达，会导致参与细胞增殖的β-连环蛋白（β-catenin）与细胞周期蛋白D1（cyclin D1）的表达水平升高。研究证实miR-200a可直接靶向β-连环蛋白的信使核糖核酸（mRNA），从而抑制其翻译过程，并阻断与肿瘤发生密切相关的β-连环蛋白-Wnt信号通路。在人类脑膜瘤样本中，miR-200a的下调与β-连环蛋白的上调呈显著正相关。综上，miR-200a可通过调控E-钙粘蛋白及β-连环蛋白-Wnt信号通路，在脑膜瘤中发挥多功能肿瘤抑制性微小核糖核酸的作用。本研究揭示了一条此前未被阐明的、参与脑膜瘤发生发展的信号级联反应，并阐明了miR-200a与Wnt信号通路间的新型分子互作，从而为脑膜瘤的新型治疗策略提供了理论依据。本研究共纳入14份脑膜瘤肿瘤样本，并以3份蛛网膜组织样本作为对照。每份样本均设置2次技术重复。数据标准化与预处理过程包含对技术重复数据的合并。下表展示了经分位数标准化（quantile-normalized）后的数据集。