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.