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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
The effect of miR-7 on behavior and global protein expression in glioma cell lines
Ze Jun Lu1, Sheng Yong Liu, Yu Qin Yao
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P R China.
Abstract:
Malignant glioma is a common cancer of the nervous system. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant glioma has remained dismal. MicroRNAs are noncoding RNAs that inhibit the expression of their targets in a sequence-specific manner, and a few have been shown to act as oncogenes or tumor suppressors. Here, we aimed at exploring the precise biological role of microRNA-7 (miR-7) and the global protein changes in glioma cell lines transiently transfected with miR-7. Transfection of miR-7 into glioma cell lines causes inhibition of cell migration and invasion and suppression of tumorigenesis. Moreover, ectopic expression of miR-7 inhibits lung metastases of glioma in vivo. Among 65 protein spots with differential expression separated by 2-DE, 37 proteins were successfully identified by MS/MS analysis. Of those, the 25 downregulated proteins, which include 14-3-3ζ, eukaryotic translation initiation factor 5A (EIF5A), and annexin A4, may be downstream targets of miR-7, a finding that could elucidate some aspects of the behavior of glioma cells at the protein level. In conclusion, the absence of miR-7 function could cause downstream molecules to switch on or off, resulting in glioma development, invasion, and metastases. MiR-7-based gene treatment may be a novel anti-invasion therapeutic strategy for malignant glioma.
Insights
MicroRNA-7 (miR-7) suppresses malignant glioma progression by inhibiting cell migration, invasion, and metastasis. Restoring miR-7 function may offer a novel therapeutic strategy for glioma treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant glioma, a common nervous system cancer, has a poor patient prognosis despite therapeutic advancements.
- MicroRNAs (miRNAs) are noncoding RNAs regulating gene expression; some function as oncogenes or tumor suppressors.
- The specific role of microRNA-7 (miR-7) in glioma pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the biological role of miR-7 in glioma.
- To identify global protein changes in glioma cells following miR-7 transfection.
- To explore miR-7 as a potential therapeutic target for malignant glioma.
Main Methods:
- Glioma cell lines were transiently transfected with miR-7.
- Cell migration, invasion, and tumorigenesis were assessed.
- Differential protein expression was analyzed using 2-DE and MS/MS identification.
Main Results:
- Ectopic miR-7 expression inhibited glioma cell migration, invasion, and tumorigenesis in vitro.
- In vivo studies showed that miR-7 suppressed lung metastases of glioma.
- MS/MS analysis identified 37 differentially expressed proteins, with 25 downregulated proteins including 14-3-3ζ, EIF5A, and annexin A4, potentially downstream targets of miR-7.
Conclusions:
- Loss of miR-7 function may promote glioma development, invasion, and metastasis through dysregulation of downstream molecules.
- MiR-7 plays a critical role in controlling glioma cell behavior at the protein level.
- MiR-7-based gene therapy presents a promising anti-invasion strategy for malignant glioma.
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