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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-146b inhibits glioma cell migration and invasion by targeting MMPs
Hongping Xia1, Yanting Qi, Samuel S Ng
1Integrative Chemical Biology Laboratory, Institute of Molecular Technology, Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
Abstract:
MicroRNAs (miRNAs) are a class of endogenous, small non-protein coding single-stranded RNA molecules, which are crucial post-transcriptional regulators of gene expression. Previous studies have shown that miRNAs participate in a wide range of biological functions and play important roles in various human diseases including glioma. However, the role of miRNAs in mediating glioblastoma cell migration and invasion has not been elucidated. Using miRNA microarray, we identified miR-146b as one of the miRNAs that is significantly dysregulated in human glioblastoma tissue. We showed that miR-146b overexpression by transfection with the precursor miR-146b, or knock-down by Locked Nucleic Acid (LNA)-modified anti-miR-146b, has no effect on the growth of human glioblastoma U373 cells. However, precursor miR-146b transfection significantly reduced the migration and invasion of U373 cells, while LNA-anti-miR-146b transfection generated the opposite result. Furthermore, we discovered that a matrix metalloproteinase gene, MMP16, is one of the downstream targets of miR-146b. Taken together, our findings suggest that miR-146b is involved in glioma cell migration and invasion by targeting MMPs, and implicate miR-146b as a metastasis-inhibiting miRNA in glioma.
Insights
MicroRNAs (miRNAs) regulate gene expression and are implicated in glioma. This study found miR-146b inhibits glioblastoma cell migration and invasion by targeting matrix metalloproteinases.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
- miRNAs are implicated in various human diseases, including glioma.
- The specific role of miRNAs in glioblastoma cell migration and invasion remains unclear.
Purpose of the Study:
- To investigate the role of dysregulated miRNAs in glioblastoma.
- To elucidate the function of miR-146b in glioblastoma cell migration and invasion.
- To identify downstream targets of miR-146b involved in glioma progression.
Main Methods:
- miRNA microarray analysis of human glioblastoma tissue.
- Transfection of glioblastoma U373 cells with precursor miR-146b and anti-miR-146b.
- Assessment of cell growth, migration, and invasion.
- Identification of downstream gene targets using molecular techniques.
Main Results:
- miR-146b was significantly dysregulated in human glioblastoma.
- miR-146b overexpression reduced glioblastoma cell migration and invasion.
- miR-146b knockdown increased cell migration and invasion.
- Matrix metalloproteinase 16 (MMP16) was identified as a direct target of miR-146b.
Conclusions:
- miR-146b plays a critical role in regulating glioblastoma cell migration and invasion.
- miR-146b exerts its function by targeting matrix metalloproteinases, such as MMP16.
- miR-146b acts as a metastasis-inhibiting miRNA in glioma, suggesting its potential as a therapeutic target.
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