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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
Differential expression of MicroRNAs in patients with glioblastoma after concomitant chemoradiotherapy
Edmond Changkyun Park1, Giwon Kim, Jongsun Jung
1Division of Life Science, Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea.
Abstract:
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, and notorious for resistance to chemoradiotherapy. MicroRNAs (miRNAs) are significantly involved in the initiation and progression of numerous cancers; however, the role of miRNAs in recurrence of tumors remains unknown. Here we tried to identify novel miRNAs that are differentially expressed in recurrent GBM. Tissue samples were obtained from patients with primary and recurrent GBM treated with chemoradiotherapy, and the expression changes of miRNAs were measured by microarray. A total of 318 miRNAs were expressed in the GBM patients. The expression of 43 miRNAs were significantly altered at least 2-fold in primary and recurrent GBMs. Bioinformatic analysis revealed that the differentially expressed miRNAs and their putative target genes were mainly involved in cell death, cellular development, and cellular growth and proliferation, which are the key regulators for stem cells. Pathway analysis supported that the miRNAs may regulate signaling associated with induction and maintenance of cancer and stem cell, such as p53, ErbB1, Notch, Wnt, and TGF-β signaling pathways. These data suggest that, in recurrent GBM, growth factor and anti-apoptotic signalings for cancer cell growth and proliferation are regulated by miRNAs. Our findings will aid future research in understanding the pathophysiology of recurrent GBM and identifying diagnostic markers and/or therapeutic targets for recurrence of GBM.
Insights
Researchers identified 43 microRNAs (miRNAs) altered in recurrent glioblastoma multiforme (GBM), a deadly brain cancer. These miRNAs regulate key pathways involved in cancer stem cell growth and survival, offering potential therapeutic targets for GBM recurrence.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor known for treatment resistance.
- MicroRNAs (miRNAs) play roles in cancer initiation and progression, but their function in tumor recurrence is unclear.
Purpose of the Study:
- To identify novel microRNAs (miRNAs) with differential expression in recurrent GBM.
- To elucidate the role of these miRNAs in GBM pathophysiology and recurrence.
Main Methods:
- Microarray analysis of miRNA expression in primary and recurrent GBM tissue samples from patients treated with chemoradiotherapy.
- Bioinformatic and pathway analyses to identify functions and signaling pathways regulated by differentially expressed miRNAs.
Main Results:
- A total of 318 miRNAs were detected; 43 miRNAs showed significant (≥2-fold) expression changes between primary and recurrent GBM.
- Differentially expressed miRNAs and their targets are primarily involved in cell death, development, growth, and proliferation, crucial for cancer stem cells.
- Pathway analysis indicated regulation of key signaling pathways including p53, ErbB1, Notch, Wnt, and TGF-β.
Conclusions:
- MicroRNAs regulate growth factor and anti-apoptotic signaling pathways in recurrent GBM.
- These findings contribute to understanding GBM pathophysiology and may identify diagnostic markers or therapeutic targets for GBM recurrence.
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