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miR-603 promotes glioma cell growth via Wnt/β-catenin pathway by inhibiting WIF1 and CTNNBIP1
Mian Guo1, Xiaoming Zhang1, Guangzhi Wang2
1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
Abstract:
Gliomas are the most common and deadly type of brain tumor. In spite of progressive treatments, patient prognosis has not improved significantly. MicroRNAs are considered promising candidates for glioma therapy. MiR-603 was found overexpressed in both glioma tissues and cell lines. MiR-603 promoted cell proliferation, cell cycle progression and neurosphere formation. Conversely, inhibition of miR-603 remarkably reduced these effects. We confirmed that WIF1 and CTNNBIP1 are bona fide targets of miR-603. The negative correlation between miR-603 and these molecules' expression was shown by Pearson correlation in 50 primary glioma tissue samples. Furthermore, overexpression of miR-603 promoted nuclear β-catenin levels and TOPflash luciferase activity, indicating that miR-603 activates the Wnt/β-catenin signaling pathway. Our in vivo results confirmed the positive role of miR-603 in glioma development. We demonstrate that miR-603 regulates glioma development via its WIF1 and CTNNBIP1 targets, which suggests that miR-603 may be a promising candidate for therapeutic applications in glioma treatment.
Insights
MicroRNAs, specifically miR-603, show promise for treating deadly brain tumors called gliomas. This study found miR-603 promotes glioma growth by activating the Wnt/β-catenin pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gliomas represent the most prevalent and lethal form of brain tumors.
- Current treatments offer limited improvement in patient prognosis.
- MicroRNAs are emerging as potential therapeutic agents for glioma treatment.
Purpose of the Study:
- To investigate the role of microRNA-603 (miR-603) in glioma development.
- To identify the molecular targets and signaling pathways regulated by miR-603 in gliomas.
- To evaluate the therapeutic potential of targeting miR-603 in glioma treatment.
Main Methods:
- Expression analysis of miR-603 in glioma tissues and cell lines.
- Functional assays to assess the impact of miR-603 on cell proliferation, cell cycle, and neurosphere formation.
- Target validation using luciferase assays and correlation analysis with WIF1 and CTNNBIP1 expression.
- Investigation of the Wnt/β-catenin signaling pathway activation.
- In vivo studies to confirm the role of miR-603 in glioma development.
Main Results:
- MiR-603 was significantly overexpressed in glioma tissues and cell lines.
- Overexpression of miR-603 enhanced glioma cell proliferation, cell cycle progression, and neurosphere formation.
- WIF1 and CTNNBIP1 were identified as direct targets of miR-603, with inverse expression correlation.
- MiR-603 was shown to activate the Wnt/β-catenin signaling pathway.
- In vivo experiments confirmed miR-603's positive contribution to glioma development.
Conclusions:
- MiR-603 plays a crucial role in promoting glioma development and progression.
- The oncogenic function of miR-603 is mediated through its regulation of WIF1 and CTNNBIP1, and activation of the Wnt/β-catenin pathway.
- MiR-603 represents a potential therapeutic target for glioma treatment.
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