microRNA profiles of schwannomas

MicroRNAs (miRNAs) negatively regulate protein-coding genes at the post-transcriptional level and are critical in tumorigenesis. Schwannomas develop from proliferation of dedifferentiated Schwann cells, which normally wrap around nerve fibers to help support and insulate nerves. In this study, we carried out high-throughput miRNA expression profiling of human vestibular schwannomas using an array representing 407 known miRNAs in order to explore the role of miRNAs in tumor growth. Twelve miRNAs were found to be significantly deregulated in tumor samples as compared with control nerve tissue, defining a schwannoma-typical signature. Among these miRNAs, we focused on miR-7 which was one of the most downregulated in these tumors and has several known oncogene targets, including mRNAs for epidermal growth factor receptor (EGFR) and p21-activated kinase 1 (Pak1). We found that overexpression of miR-7 inhibited schwannoma cell growth both in culture and in a xenograft tumor model in vivo, which correlated with downregulation of these signaling pathways. Furthermore, we identified a novel direct target of miR-7, the mRNA for associated cdc42 kinase 1 (Ack1), with the expression levels of miR-7 and Ack1 being inversely correlated in human schwannoma samples. These findings are the first analyzing miRNA profiles of schwannomas and support a “tumor suppressor” function for miR-7 in these tumors by targeting proteins in three major oncogenic pathways, EGFR, Pak1, and Ack1. Moreover, our result also suggest that miR-7 may serve as a potential therapeutic molecule for schwannomas and that drugs which inhibit these signaling pathways could suppress growth of these benign tumors. Schwannoma tumor samples are compared to nerve controls