miR-200a regulation of the Wnt signaling in meningioma tumorigenesis

A number of microRNAs (miRNAs) are dysregulated in cancer and they can exert critical roles in initiation and progression of various tumors. Meningiomas are derived from arachnoidal cells associated with brain meninges and frequently associated with loss of the neurofibromatosis 2 (NF2) gene. Here, we define a human meningioma-typical miRNA profile and characterize effects of one miRNA, miR-200a which is markedly downregulated in these tumors. Elevation of levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. This upregulation of miR-200a was associated with decreased expression of transcription factors, ZEB1 and SIP1, with consequently increased E-cadherin expression. An inverse correlation was also found between downregulation of miR-200a in meningiomas and increased expression of β-catenin and cyclin D1, with miR-200a targeting of the β-catenin mRNA and inhibiting Wnt signaling. miR-200a appears to act as a multi-functional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and β-catenin 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.