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Updated: Jun 4, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas
1Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Abstract:
Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
Insights
MicroRNAs like miR-21 drive glioma invasion by disrupting Spry2 regulation in PTEN-deficient tumors. Decreased Spry2 protein in gliomas suggests miR-21 as a therapeutic target for improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gliomas are highly invasive brain tumors with poor prognosis.
- Understanding the molecular basis of glioma invasion is crucial for developing effective treatments.
- MicroRNAs (miRNAs) are increasingly recognized for their role in cancer progression and metastasis.
Purpose of the Study:
- To investigate the role of microRNA deregulation in glioma invasion.
- To elucidate the molecular mechanisms underlying the onset of glioma invasiveness.
- To identify potential therapeutic targets for combating glioma malignancy.
Main Methods:
- Analysis of miR-21 expression and its impact on the Ras/MAPK signaling pathway.
- Investigation of Spry2 as a target of miR-21.
- Correlation of Spry2 protein levels with miR-21 levels in human glioma tissues.
- Assessment of the influence of tumor microenvironmental factors (hyaluronan, growth factors) on miR-21 upregulation in PTEN-deficient cells.
Main Results:
- Aberrant miR-21 expression disrupts the Ras/MAPK signaling pathway via Spry2, promoting glioma invasion.
- miR-21 upregulation is associated with PTEN deficiency and triggered by microenvironmental factors.
- Significantly decreased Spry2 protein levels were observed in invasive WHO grade II-IV gliomas but not in normal or non-invasive grade I tissues.
- Spry2 protein levels showed an inverse correlation with miR-21 levels, independent of mRNA levels, indicating post-transcriptional regulation.
Conclusions:
- Post-transcriptional regulation of Spry2 by miR-21 plays a critical role in the malignant progression of human gliomas.
- Spry2 represents a potential novel therapeutic target for glioma treatment.
- Targeting miR-21 or restoring Spry2 function could offer new avenues for glioma therapy.
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