title: Posttranscriptional deregulation of signaling pathways in meningioma subtypes by differential expression of miRNAs.
abstract: BACKGROUND
  Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the affected signaling pathways.
  
  
  METHODS
  In this study, we compared expression of 1205 miRNAs in different meningioma grades and histological subtypes using microarrays and independently validated deregulation of selected miRNAs with quantitative real-time PCR. Clinical utility of a subset of miRNAs as biomarkers for World Health Organization (WHO) grade II meningioma based on quantitative real-time data was tested. Potential targets of deregulated miRNAs were discovered with an in silico analysis.
  
  
  RESULTS
  We identified 13 miRNAs deregulated between different subtypes of benign meningiomas, and 52 miRNAs deregulated in anaplastic meningioma compared with benign meningiomas. Known and putative target genes of deregulated miRNAs include genes involved in epithelial-to-mesenchymal transition for benign meningiomas, and Wnt, transforming growth factor-β, and vascular endothelial growth factor signaling for higher-grade meningiomas. Furthermore, a 4-miRNA signature (miR-222, -34a*, -136, and -497) shows promise as a biomarker differentiating WHO grade II from grade I meningiomas with an area under the curve of 0.75.
  
  
  CONCLUSIONS
  Our data provide novel insights into the contribution of miRNAs to the phenotypic spectrum in benign meningiomas. By deregulating translation of genes belonging to signaling pathways known to be important for meningioma genesis and progression, miRNAs provide a second in line amplification of growth promoting cellular signals. MiRNAs as biomarkers for diagnosis of aggressive meningiomas might prove useful and should be explored further in a prospective manner.
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Nicole
authors: N
authors: Ludwig
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Yoo-Jin
authors: YJ
authors: Kim
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Sabine C
authors: SC
authors: Mueller
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Christina
authors: C
authors: Backes
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Tamara V
authors: TV
authors: Werner
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Valentina
authors: V
authors: Galata
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Elke
authors: E
authors: Sartorius
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Rainer M
authors: RM
authors: Bohle
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Andreas
authors: A
authors: Keller
authors: Department of Human Genetics Medical School, Saarland University, Homburg/Saar, Germany (N.L., S.C.M., C.B., T.V.W., V.G., E.M.); Institute of Pathology Medical School, Saarland University, Homburg/Saar, Germany (Y.-J.K., E.S., R.M.B.); Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany (S.C.M., C.B., V.G., A.K.).
authors: Eckart
authors: E
authors: Meese
mesh_terms: D014408:Biomarkers, Tumor; D018450:Disease Progression; D006801:Humans; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D060787:Neoplasm Grading; D012323:RNA Processing, Post-Transcriptional; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: histological subtypes; meningioma; miRNA; qRT-PCR