MicroRNA-485-5p attenuates cell proliferation in glioma by directly targeting paired box 3
Ren Wang1, Xiaohua Zuo2,3, Kai Wang4
1Department of Pediatric Surgery, Huai'an Women and Children's Hospital Huai'an 223002, Jiangsu, PR China.
Abstract:
MicroRNA-485-5p (miR-485-5p) has been reported to be involved in the development and progression of human cancers; however, its role in glioma remains unclear. In the present study, we found that miR-485-5p was significantly down-regulated in both glioma tissues and cell lines. Functional experiments indicated that enhanced expression of miR-485-5p attenuated glioma cell proliferation in vitro and in vivo, and induced glioma cells cycle arrest in G1. MiR-485-5p was found to directly bind to the 3'-UTR of paired box 3 (PAX3) and decrease its expression of protein level, which further inhibits the proliferation of glioma. The decreasing of PAX3 was found to lead to the accumulation of p-JNK. Mechanistic studies revealed that restoring the expression of PAX3 alleviated miR-485-5p-induced inhibition of proliferation of glioma cells. Taken together, these findings suggest that PAX3 modulation by miR-485-5p has an important role in regulating glioma proliferation, and miR-485-5p might be a novel therapeutic target for glioma.
Insights
MicroRNA-485-5p (miR-485-5p) is down-regulated in glioma. Restoring miR-485-5p inhibits glioma cell proliferation by targeting PAX3, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-485-5p (miR-485-5p) is implicated in human cancers, but its function in glioma is not well understood.
- Glioma is a primary brain tumor with significant morbidity and mortality.
- Understanding the molecular mechanisms underlying glioma progression is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of miR-485-5p in glioma development and progression.
- To identify the molecular targets and pathways regulated by miR-485-5p in glioma.
- To evaluate the therapeutic potential of miR-485-5p in glioma.
Main Methods:
- Analysis of miR-485-5p expression in glioma tissues and cell lines.
- In vitro and in vivo functional assays to assess the effect of miR-485-5p on glioma cell proliferation.
- Luciferase reporter assays and Western blotting to confirm the direct binding of miR-485-5p to PAX3 and its effect on protein expression.
- Investigation of downstream signaling pathways, including JNK phosphorylation.
Main Results:
- miR-485-5p was significantly downregulated in glioma tissues and cell lines.
- Overexpression of miR-485-5p suppressed glioma cell proliferation in vitro and in vivo and induced G1 cell cycle arrest.
- miR-485-5p directly targets the 3'-UTR of PAX3, reducing its protein expression.
- Decreased PAX3 expression led to p-JNK accumulation.
- Restoration of PAX3 expression rescued the inhibitory effects of miR-485-5p on glioma cell proliferation.
Conclusions:
- miR-485-5p acts as a tumor suppressor in glioma by inhibiting cell proliferation.
- The miR-485-5p/PAX3 axis plays a critical role in regulating glioma progression.
- miR-485-5p represents a promising novel therapeutic target for glioma treatment.
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