MTF2 facilitates the advancement of osteosarcoma through mediating EZH2/SFRP1/Wnt signaling
Background: Osteosarcoma is a soft tissue tumor with a high risk of recurrence and significant metastatic potential. Metal response element binding transcription factor 2 (MTF2) has been shown to play various roles in human tissues. However, the specific functions and mechanisms of MTF2 in osteosarcoma remain unexplored. This study aims to investigate the role of MTF2 in osteosarcoma and its associated response mechanisms.
Methods: Bioinformatics tools were used to analyze differential MTF2 expression in osteosarcoma tissues. Western blotting was employed to assess MTF2 expression in osteosarcoma cells. Cell proliferation, migration, and invasion were measured using the Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2′-deoxyuridine (EDU) staining, wound healing, and transwell assays, respectively. Flow cytometry was used to assess cellular apoptosis. Western blot analysis also measured the expression of proteins related to epithelial-mesenchymal transition (EMT), apoptosis, and the EZH2/SFRP1/Wnt signaling pathway. The interaction between MTF2 and EZH2 was confirmed through co-immunoprecipitation (Co-IP).
Results: MTF2 expression was found to be elevated in both osteosarcoma tissues and cells. Silencing MTF2 inhibited cell proliferation, migration, and invasion while promoting apoptosis. MTF2 was shown to directly bind to EZH2, and its downregulation reduced EZH2 expression, activated SFRP1 expression, and blocked Wnt signaling in osteosarcoma cells. Overexpression of EZH2 or treatment with the SFRP1 antagonist WAY-316606 partially reversed the effects of MTF2 knockdown on SFRP1/Wnt signaling and the biological behaviors of osteosarcoma cells.
Conclusions: MTF2 may promote osteosarcoma progression by downregulating SFRP1, thereby activating Wnt signaling through its interaction with EZH2.