miR-506-5p targets MAPK7 to impede glioma growth and invasion through suppressing epithelial-mesenchymal transition and matrix metalloproteinases

Background: Glioma remains a challenging malignancy with limited therapeutic options, and the underlying molecular mechanisms driving its progression are not fully understood. Although miR-506-5p has been implicated in various tumors, its role in glioma progression and the associated mechanisms warrant further investigation. This study aims to explore whether miR-506-5p suppresses glioma growth and invasion by targeting MAPK7, thereby regulating matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT).

Methods: Expression levels of miR-506-5p and MAPK7 in glioma tissues and cell lines were examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The direct interaction between miR-506-5p and MAPK7 was validated using dual-luciferase reporter assays. Gain- and loss-of-function approaches were employed in U87 glioma cells, followed by 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and Transwell assays to assess proliferation, migration, and invasion. Western blotting was performed to evaluate MAPK7, MMPs, and EMT-related markers. Rescue experiments were conducted to confirm the involvement of MAPK7 in miR-506-5p-mediated effects. Additionally, a xenograft model was established to evaluate the anti-tumor activity of miR-506-5p in vivo.

Results: MiR-506-5p expression was significantly downregulated, while MAPK7 expression was markedly upregulated, in glioma tissues and cell lines compared with controls. Dual-luciferase reporter assays confirmed that miR-506-5p directly targeted the 3'-UTR of MAPK7. Overexpression of miR-506-5p suppressed cell proliferation, migration, invasion, and EMT, accompanied by decreased expression of MAPK7, MMP9, MMP12, N-cadherin, and vimentin, and increased E-cadherin expression. Conversely, miR-506-5p knockdown produced opposite effects. Rescue experiments demonstrated that MAPK7 overexpression reversed the suppressive effects induced by miR-506-5p, whereas MAPK7 knockdown reversed the pro-tumorigenic effects of miR-506-5p inhibition. In vivo, miR-506-5p overexpression significantly inhibited xenograft tumor growth, reduced Ki-67 positivity, and recapitulated the molecular changes observed in vitro.

Conclusions: MiR-506-5p functions as a tumor suppressor in glioma by directly targeting MAPK7, thereby inhibiting MMP expression and EMT to suppress tumor growth, migration, and invasion. The miR-506-5p/MAPK7 axis represents a potential therapeutic target for glioma intervention.