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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients
1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. slaby@mou.cz
Abstract:
MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies showed altered expression levels of several microRNAs in glioblastomas. In this study, we examined the expression levels of selected microRNAs in 22 primary glioblastomas and six specimens of adult brain tissue by real-time PCR method. In addition, we examined methylation status of MGMT promoter by methylation-specific real-time PCR, as this has been shown to be a predictive marker in glioblastomas. MGMT methylation status was not correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiR-221 (p=0.016), miR-222 (p=0.038), miR-181b (p=0.036), miR-181c (p=0.043) and miR-128a (p=0.001) were significantly down-regulated in glioblastomas. The most significant change was observed for up-regulation in miR-21 expression in glioblastomas (p<0.001). MiR-181b and miR-181c were significantly down-regulated in patients who responded to RT/TMZ (p=0.016; p=0.047, respectively) in comparison to patients with progredient disease. Our data indicate for the first time that expression levels of miR-181b and miR-181c could serve as a predictive marker of response to RT/TMZ therapy in glioblastoma patients.
Insights
MicroRNAs regulate gene expression. This study found miR-181b and miR-181c down-regulation in glioblastoma patients responding to chemoradiotherapy with temozolomide (RT/TMZ), suggesting their potential as predictive biomarkers.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Altered miRNA expression is implicated in glioblastoma development.
- MGMT promoter methylation is a predictive marker for glioblastoma treatment response.
Purpose of the Study:
- To investigate the expression levels of specific microRNAs in glioblastoma.
- To explore the correlation between miRNA expression, MGMT methylation, and response to chemoradiotherapy with temozolomide (RT/TMZ).
- To identify potential miRNA biomarkers for predicting RT/TMZ treatment efficacy in glioblastoma.
Main Methods:
- Real-time PCR was used to quantify miRNA expression in 22 primary glioblastomas and 6 adult brain tissue specimens.
- Methylation-specific real-time PCR assessed MGMT promoter methylation status.
- Expression data were analyzed in correlation with clinical response to RT/TMZ.
Main Results:
- Several microRNAs (miR-221, miR-222, miR-181b, miR-181c, miR-128a) were significantly down-regulated in glioblastomas.
- miR-21 expression was significantly up-regulated in glioblastomas.
- MGMT methylation status did not correlate with RT/TMZ response.
- Down-regulation of miR-181b and miR-181c was significantly associated with response to RT/TMZ compared to progressive disease.
Conclusions:
- miR-181b and miR-181c expression levels may serve as predictive biomarkers for response to chemoradiotherapy with temozolomide in glioblastoma patients.
- These findings highlight the potential role of specific microRNAs in guiding glioblastoma treatment decisions.
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