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Updated: Apr 18, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
MicroRNA-27a distinguishes glioblastoma multiforme from diffuse and anaplastic astrocytomas and has prognostic value
Mónica Rivera-Díaz1, Miguel A Miranda-Román2, Daniel Soto2
1Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico San Juan, Puerto Rico 00935 ; Department of Biochemistry, Medical Sciences Campus, University of Puerto Rico San Juan, Puerto Rico 00935.
Abstract:
MicroRNAs (miRNAs) are a class of small noncoding RNAs that bind to 3'-untranslated (UTR) regions of target messenger RNAs to regulate protein synthesis. Reports have suggested that a set of specific miRNAs may be used as diagnostic and/or prognostic markers for astrocytoma grading. However, there are few studies of the specific miRNAs differentially expressed in each astrocytoma grade. MiRNA-containing total RNA was isolated from archived formalin-fixed, paraffin-embedded (FFPE) samples from WHO grade II-IV astrocytoma patients. The RNA was labeled and hybridized to Affymetrix miRNA 2.0 arrays. Statistical analysis identified several miRNAs differentially expressed in each astrocytoma grade. In particular, miR-27a, miR-210, and miR-1225-5p expression levels were able to differentiate grade IV from grade II and III astrocytomas as confirmed by real-time PCR. Kaplan-Meier survival analysis showed that disease progression occurred faster for Glioblastoma Multiforme (GBM) patients with a lower miR-27a expression level. Transfection of CRL-1690 GBM human cancer cells with a miR-27a oligonucleotide inhibitor followed by Real-time PCR identified six potential miR-27a target genes. Furthermore, the miR-27a oligonucleotide inhibitor induced CRL-1690 cell apoptosis. Taken together, our results provide additional miRNA signatures for distinguishing GBM from lower astrocytoma grades and suggest miR-27a as a prognostic and therapeutic target for GBM.
Insights
Specific microRNAs (miRNAs) can distinguish high-grade astrocytomas from lower grades. MiR-27a shows potential as a prognostic and therapeutic target for Glioblastoma Multiforme (GBM), impacting disease progression and cell apoptosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) are key regulators of protein synthesis.
- Specific miRNAs are implicated as potential biomarkers for astrocytoma grading.
- Limited research exists on miRNA expression differences across astrocytoma grades.
Purpose of the Study:
- To identify differentially expressed miRNAs in astrocytoma grades II-IV.
- To evaluate the diagnostic and prognostic potential of specific miRNAs in astrocytoma.
- To investigate the therapeutic potential of miR-27a in Glioblastoma Multiforme (GBM).
Main Methods:
- RNA isolation from formalin-fixed, paraffin-embedded (FFPE) astrocytoma samples (WHO grades II-IV).
- Affymetrix miRNA 2.0 array hybridization for miRNA expression profiling.
- Real-time PCR for validation and Kaplan-Meier survival analysis.
Main Results:
- Several miRNAs were found to be differentially expressed across astrocytoma grades.
- miR-27a, miR-210, and miR-1225-5p distinguished grade IV from grades II and III astrocytomas.
- Lower miR-27a expression correlated with faster disease progression in GBM patients.
Conclusions:
- Identified miRNA signatures can differentiate GBM from lower-grade astrocytomas.
- miR-27a demonstrates potential as a prognostic biomarker for GBM.
- miR-27a inhibition induced apoptosis in GBM cells, suggesting therapeutic value.
