Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c

Altay Burak Dalan,Sukru Gulluoglu,Ugur Ture,Aysegul Kuskucu,Oguz Ozturk,Omer Faruk Bayrak,Emre Can Tuysuz,Cumhur Kaan Yaltirik

doi:10.1186/s12885-017-3198-4

Altay Burak Dalan, Sukru Gulluoglu + Show 6 more

Open Access

https://doi.org/10.1186/s12885-017-3198-4

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Journal: BMC Cancer	Publication Date: Mar 21, 2017
Citations: 26	License type: open-access

Affiliation: Yeditepe University Hospital, Yeditepe University

Abstract

BackgroundAlthough 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.MethodsFourteen 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.ResultsWith 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.ConclusionsOur 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.

Highlights

Meningioma is a common disease, there is a lack of understanding of the underlying molecular mechanisms behind its initiation and progression
Of 48,226 genes that were checked for expression, 1257 genes were found to be upregulated and 2496 were found to be downregulated as a result of whole transcriptome microarray (Additional file 2: Figure S1)
Deregulated micro RNA (miRNA) and mRNAs were analyzed for their collective effect on important molecular and cellular events (Table 1)

Summary

Introduction

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. Meningiomas account for 30% of primary brain tumors and occur at a rate of 5 per 100,000 individuals [1]. There is a lack of understanding of underlying molecular mechanisms behind their initiation and progression. To elucidate some of these mechanisms, we used combined miRNA-mRNA transcriptome analysis to discover novel genes and networks in meningiomas. We describe integrated analysis of gene networks that might play an important role in the initiation and progression of meningiomas, with emphasis on the downregulation of tumor suppressor PTX3 via miR-29c

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