Experiment ID | EXP00109 |
Reference | Title: miRNA-7 attenuation in Schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways. Author: Saydam O, Senol O, Würdinger T, Mizrak A, Ozdener GB, Stemmer-Rachamimov AO,Yi M, Stephens RM, Krichevsky AM, Saydam N, Brenner GJ, Breakefield XO. Journal: Cancer Res. 2011 Feb 1;71(3):852-61. doi: 10.1158/0008-5472.CAN-10-1219. Epub2010 Dec 13. Abstract: Micro RNAs (miRNA) negatively regulate protein-coding genes at theposttranscriptional level and are critical in tumorigenesis. Schwannomas develop from proliferation of dedifferentiated Schwann cells, which normally wrap nervefibers to help support and insulate nerves. In this study, we carried outhigh-throughput miRNA expression profiling of human vestibular schwannomas byusing an array representing 407 known miRNAs to explore the role of miRNAs intumor growth. Twelve miRNAs were found to be significantly deregulated in tumorsamples as compared with control nerve tissue, defining a schwannoma-typicalsignature. Among these miRNAs, we focused on miR-7, which was one of the mostdownregulated in these tumors and has several known oncogene targets, includingmRNAs for epidermal growth factor receptor (EGFR) and p21-activated kinase 1(Pak1). We found that overexpression of miR-7 inhibited schwannoma cell growthboth in culture and in xenograft tumor models in vivo, which correlated withdownregulation of these signaling pathways. Furthermore, we identified a noveldirect target of miR-7, the mRNA for associated cdc42 kinase 1 (Ack1), with theexpression levels of miR-7 and Ack1 being inversely correlated in humanschwannoma samples. These results represent the first miRNA profiling ofschwannomas and the first report of a tumor suppressor function for miR-7 inthese tumors that is mediated by targeting the EGFR, Pak1, and Ack1 oncogenes.Our findings suggest miR-7 as a potential therapeutic molecule for schwannomatreatment, and they prompt clinical evaluation of drugs that can inhibit theEGFR, Pak1, and Ack1 signaling pathways to treat this tumor type. PMID: 21156648 |
Expressiion Profile | Description: microRNA profiles of schwannomas Organism: Homo sapiens GEO ID: GSE24390 Platform: GPL7436 Number of samples: 24 |
Design and Sample | Cancer Type: brain cancer Cancer SubType: Schwannoma tumors Cell Line: N/D Experimental Design: cancer vs normal Case Sample: Schwannoma tumors Control Sample: control Num of Case: 20 Num of Control: 4 Quantification Software: Limma Num of miRNAs: 342 |
Identification | Num of Up: 12 Num of Down: 2 |