Long noncoding RNA OIP5-AS1 targets Wnt-7b to affect glioma progression via modulation of miR-410
Wei-Li Sun1, Tian Kang2, Yuan-Yu Wang3
1Department of Rehabilitation, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Abstract:
The present study was undertaken to investigate the underlying mechanisms of long noncoding RNA OIP5-AS1 via regulating miR-410 to modulate Wnt-7b in the progression of glioma. To address this problem, we measured the expression of OIP5-AS1 and miR-410 in glioma tissues by qRT-PCR. Glioma U87 cells were transfected with OIP5-AS1 siRNA or miR-410 inhibitors. The targeting relationships among miR-410, OIP5-AS1 and Wnt-7b were verified by luciferase reporter assays. Western blotting was employed to determine the expression of Wnt-7b/β-catenin pathway-related proteins, while MTT, flow cytometry, Transwell assays and wound-healing assays were used to measure the biological characteristics of glioma cells. The results showed that OIP5-AS1 expression was higher and miR-410 was lower in glioma tissues. Luciferase reporter assays confirmed a targeting relationship between OIP5-AS1 and miR-410, as well as between miR-410 and Wnt-7b. Silencing OIP5-AS1 reduced cell proliferation, invasion and migration of glioma U87 cells and led to depressed expression levels of miR-410, Wnt-7b, p-β-catenin, GSK-3β-pS9, c-Myc and cyclin D1. Furthermore, down-regulation of OIP5-AS1 induced G0/G1 phase cell cycle arrest and apoptosis of glioma cells. Inhibitors of miR-410 abolished the biological effects of OIP5-AS1 siRNA in glioma cells. In vivo, OIP5-AS1 knockdown also inhibited tumor growth. Taken together, this research suggested that silencing OIP5-AS1 may specifically block the Wnt-7b/β-catenin pathway via targeted up-regulating miR-410, thereby inhibiting growth, invasion and migration while promoting apoptosis in glioma cells.
Insights
Silencing long noncoding RNA OIP5-AS1 inhibits glioma progression by up-regulating miR-410, blocking the Wnt-7b/β-catenin pathway, and promoting apoptosis. This offers a potential therapeutic strategy for glioma treatment.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Glioma is a common primary brain tumor with complex molecular mechanisms.
- Long noncoding RNAs (lncRNAs) play crucial roles in cancer progression.
- OIP5-AS1 has been implicated in various cancers, but its role in glioma requires further elucidation.
Purpose of the Study:
- To investigate the role of OIP5-AS1 in glioma progression.
- To explore the regulatory mechanism of OIP5-AS1 involving miR-410 and Wnt-7b.
- To assess the therapeutic potential of targeting OIP5-AS1 in glioma.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure gene expression in glioma tissues.
- Cell transfection with OIP5-AS1 siRNA and miR-410 inhibitors.
- Luciferase reporter assays to confirm targeting relationships.
- Western blotting for protein expression analysis.
- Cell proliferation, invasion, migration, cell cycle, and apoptosis assays (MTT, flow cytometry, Transwell, wound-healing).
- In vivo tumor growth inhibition studies.
Main Results:
- OIP5-AS1 was upregulated, while miR-410 was downregulated in glioma tissues.
- OIP5-AS1 directly targets miR-410, and miR-410 targets Wnt-7b.
- Silencing OIP5-AS1 inhibited glioma cell proliferation, invasion, and migration.
- OIP5-AS1 knockdown led to decreased expression of Wnt-7b and downstream proteins in the Wnt-7b/β-catenin pathway.
- Downregulation of OIP5-AS1 induced cell cycle arrest and apoptosis, and inhibited tumor growth in vivo.
- miR-410 inhibitors reversed the effects of OIP5-AS1 silencing.
Conclusions:
- OIP5-AS1 promotes glioma progression by sponging miR-410 and activating the Wnt-7b/β-catenin pathway.
- Targeting OIP5-AS1 represents a potential therapeutic strategy for glioma.
- The OIP5-AS1/miR-410/Wnt-7b axis is a critical regulator of glioma cell behavior.
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