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Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3
Altay Burak Dalan1, Sukru Gulluoglu2,3, Emre Can Tuysuz2,3
1Department of Biochemistry, Yeditepe University Medical School, Istanbul, Turkey.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Researchers identified key molecular players in meningioma development. Inhibiting miR-29c in meningioma cells increased PTX3, reduced cell viability, and induced apoptosis, revealing potential therapeutic targets for this common brain tumor.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Meningioma is a common primary brain tumor with poorly understood molecular drivers.
- Identifying molecular mechanisms is crucial for understanding meningioma initiation and progression.
Purpose of the Study:
- To investigate dysregulated genes and networks in meningiomas using integrated miRNA-mRNA transcriptome analysis.
- To uncover potential molecular targets for meningioma treatment.
Main Methods:
- Analysis of miRNA and whole transcriptome microarrays from meningioma samples and cell lines.
- Bioinformatic analysis to identify dysregulated genes, miRNAs, and pathways.
- Functional assays including miRNA inhibition, apoptosis, and cell viability tests.
Main Results:
- Identification of 3753 dysregulated genes and 891 dysregulated miRNAs.
- Top affected pathways include inflammation, cancer, and cellular growth/survival.
- The oncosuppressor PTX3 was downregulated and inversely correlated with miR-29c.
- Inhibition of miR-29c upregulated PTX3, induced apoptosis, and decreased meningioma cell viability.
- Correlation of specific genes and miRNAs (e.g., miR-29c, PTX3) with clinicopathological features.
Conclusions:
- The study provides the first integrated mRNA-miRNA analysis in meningiomas.
- miR-29c-3p and PTX3 show an inverse correlation, suggesting PTX3 is regulated by miR-29c-3p.
- Identified miR-29c and PTX3 as potential therapeutic targets and clinicopathological markers for meningioma.
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