The online version of this article (doi:10.1186/s12885-017-3198-4) contains supplementary material, which is available to authorized users.
Although meningioma is a common disease, there is a lack of understanding of the underlying molecular mechanisms behind its initiation and progression. We used combined miRNA-mRNA transcriptome analysis to discover dysregulated genes and networks in meningiomas.
Fourteen fresh-frozen meningioma samples and one human meningeal cell line were analyzed by using miRNA and whole transcriptome microarray chips. Data was filtered and analyzed. Candidate miRNAs and mRNAs were selected for validation in fifty-eight patient samples. miRNA and target mRNA relationships were assessed by inhibiting miRNA in meningioma cells. Apoptosis and viability assays were also used as functional tests.
With the whole transcriptome microarray, 3753 genes were found to be dysregulated, and 891 miRNAs were found to be dysregulated as a result of miRNA microarray. Results were combined and analyzed with bioinformatics tools. Top differential pathways included those of inflammation, cancer, and cellular growth and survival. The oncosupressor PTX3 was constitutively low in meningioma samples. Moreover, PTX3 negatively correlated with miR-29c in our samples. Inhibiting miR-29c upregulated the PTX3 level, induced apoptosis of meningioma cells, and decreased cell viability. CABIN1, miR-29c, TMOD1, PTX3, RPL22, SPARCL1 and RELA were correlated with clinicopathological features in patient samples.
Our results present the first integrated mRNA-miRNA analysis in meningiomas. miR-29c-3p and PTX3 are inversely correlated in tissues and meningioma cells, hinting that PTX3 can be regulated by miR-29c-3p. Furthermore, we determined potential clinicopathological markers.
Additional file 1: Table S1. An overview of the patient cohort. Tumor location and stage definition of patient samples. Median age of patients was 55.5 and age range was 15-89. (DOCX 17 kb)12885_2017_3198_MOESM1_ESM.docx
Additional file 2: Figure S1. Array study report for gene expression microarray: Summary of the gene expression array results, scatter plot and volcano plot generated by TAC software (Affymetrix). (TIFF 355 kb)12885_2017_3198_MOESM2_ESM.tif
Additional file 3: Figure S2. Array study report for miRNA microarray: Summary of the miRNA array results, scatter plot and volcano plot generated by TAC software (Affymetrix). (TIFF 276 kb)12885_2017_3198_MOESM3_ESM.tif
Shibuya M. Pathology and Molecular Genetics of Meningioma: Recent Advances. Neurol Med Chir (Tokyo). 2015;55(Suppl 1):14–27. CrossRef
Saydam O, Shen Y, Wurdinger T, Senol O, Boke E, James MF, Tannous BA, Stemmer-Rachamimov AO, Yi M, Stephens RM, et al. Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. Mol Cell Biol. 2009;29(21):5923–40. CrossRefPubMedPubMedCentral
Kliese N, Gobrecht P, Pachow D, Andrae N, Wilisch-Neumann A, Kirches E, Riek-Burchardt M, Angenstein F, Reifenberger G, Riemenschneider MJ, et al. miRNA-145 is downregulated in atypical and anaplastic meningiomas and negatively regulates motility and proliferation of meningioma cells. Oncogene. 2013;32(39):4712–20. CrossRefPubMed
Kim Y, Kim H, Park D, Jeoung D. miR-335 Targets SIAH2 and Confers Sensitivity to Anti-Cancer Drugs by Increasing the Expression of HDAC3. Mol Cells. 2015;38(6):562–72.
Jiang H, Zhang G, Wu JH, Jiang CP. Diverse roles of miR-29 in cancer (review). Oncol Rep. 2014;31(4):1509–16. PubMed
Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007;104(40):15805–10. CrossRefPubMedPubMedCentral
Kunes P, Holubcova Z, Kolackova M, Krejsek J. Pentraxin 3(PTX 3): an endogenous modulator of the inflammatory response. Mediat Inflamm. 2012;2012:920517. CrossRef
Rubin G, Herscovici Z, Laviv Y, Jackson S, Rappaport ZH. Outcome of untreated meningiomas. Isr Med Assoc J. 2011;13(3):157–60. PubMed
- Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c
Altay Burak Dalan
Emre Can Tuysuz
Cumhur Kaan Yaltirik
Omer Faruk Bayrak
- BioMed Central
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