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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 postoperative radiotherapy sensitive and resistant patients with glioblastoma
He-Ming Wu1, Han-Dong Wang, Yong Tang
1Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
Abstract:
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more resistant to radiotherapy. However, hetero-radiosensitivity occurs in different patients. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. The study aims to examine the different microRNAs expression profiles of postoperative radiotherapy sensitive and resistant patients with GBM, to make an inquiry about their potential role and discover a certain set of radio-sensitivity markers. Three paired samples from six GBM patients who had only been treated with postoperative radiotherapy were selected, and then, they were divided into radiotherapy sensitive group and resistant group according to their overall survivals, local recurrence rates, and Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two groups were determined by the method of microarray assay. Comparing with resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were greatly downregulated in sensitive group. Among them, four miRNAs were validated by quantitative RT-PCR. The differentially expressed miRNAs and their putative target genes were revealed by bioformatic analysis to play a role in cell signaling, proliferation, aging, and death. High-enrichment pathway analysis identified that some classical pathways participated in numerous metabolic processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and PI3K-Akt signaling pathways. Our research will contribute to identifying clinical diagnostic markers and therapeutic targets in the treatment of GBM by postoperative radiotherapy.
Insights
Researchers identified specific microRNAs (miRNAs) that indicate how sensitive glioblastoma patients are to radiotherapy. These microRNA profiles could lead to new diagnostic markers and treatments for brain tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor known for its resistance to radiotherapy.
- Patient responses to radiotherapy for GBM can vary significantly, indicating underlying biological differences.
Purpose of the Study:
- To investigate microRNA (miRNA) expression profiles in GBM patients with differing sensitivities to postoperative radiotherapy.
- To identify potential miRNA biomarkers for predicting radiotherapy response and to explore their roles in GBM progression.
Main Methods:
- Microarray analysis was used to compare miRNA expression profiles between radiotherapy-sensitive and resistant GBM patient groups.
- Quantitative RT-PCR was employed to validate differentially expressed miRNAs.
- Bioinformatic analysis was performed to identify target genes and enriched pathways.
Main Results:
- Thirteen miRNAs were significantly upregulated and ten were downregulated in the radiotherapy-sensitive GBM group compared to the resistant group.
- Validated miRNAs and their predicted target genes are involved in crucial cellular processes like signaling, proliferation, aging, and death.
- Pathway analysis highlighted the involvement of cell cycle regulation pathways, including mTOR, MAPK, TGF-beta, and PI3K-Akt signaling.
Conclusions:
- The study identified distinct miRNA expression profiles associated with radiotherapy sensitivity in GBM.
- These findings suggest that specific miRNAs could serve as valuable diagnostic markers for GBM radiotherapy response.
- The identified miRNAs and pathways represent potential therapeutic targets for improving GBM treatment outcomes.
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