Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c.
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.
Department of Biochemistry, Yeditepe University Medical School, Istanbul, Turkey.
Altay Burak
AB
Dalan
Department of Medical Genetics, Yeditepe University Medical School, Istanbul, Turkey.|Department of Biotechnology, Institute of Science, Yeditepe University, Istanbul, Turkey.
Sukru
S
Gulluoglu
Department of Medical Genetics, Yeditepe University Medical School, Istanbul, Turkey.|Department of Biotechnology, Institute of Science, Yeditepe University, Istanbul, Turkey.
Emre Can
EC
Tuysuz
Department of Medical Genetics, Yeditepe University Medical School, Istanbul, Turkey.
Aysegul
A
Kuskucu
Department of Neurosurgery, Yeditepe University Medical School, Istanbul, Turkey.
Cumhur Kaan
CK
Yaltirik
Department of Molecular Medicine, Capa School of Medicine, Istanbul University, Istanbul, Turkey.
Oguz
O
Ozturk
Department of Neurosurgery, Yeditepe University Medical School, Istanbul, Turkey.
Ugur
U
Ture
Department of Medical Genetics, Yeditepe University Medical School, Istanbul, Turkey. ofbayrak@yeditepe.edu.tr.|Yeditepe Universitesi Hastanesi Genetik Tani Merkezi, Koftuncu Sokak Acıbadem mahallesi Istek Vakfi 3. Kat 34718 No: 57/1, Kadikoy, Istanbul, Turkey. ofbayrak@yeditepe.edu.tr.
Omer Faruk
OF
Bayrak
D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D000683:Serum Amyloid P-Component / Q000235:genetics*; D000099153:Pentraxins
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D035683:MicroRNAs; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C532045:MIRN29a microRNA, human
PTX3; meningioma; miR-29c; miRNA; microarray; transcriptome