MiR-145 modulation of TGF-β pathway attenuates EMT inhibition of Wilms’Tumor cell proliferation, invasion and migration

Abstract To explore the impact of miR-145 on the proliferation, migration, and invasion of Wilms' tumor G401 cells by attenuating EMT through modulation of the TGF-β pathway.A Wilms' tumor G401 cell line overexpressing miR-145 and a blank control group were established.The proliferation of Wilms' tumor cells was assessed using the CCK8 assay and colony formation experiments.The influence of miR-145 overexpression on the migration and invasion capabilities of these cells was evaluated through Transwell assays.Western blotting was used to analyze the expression of TGF-β pathway-related proteins,EMT-related proteins,and apoptosis-related proteins.Additionally,changes in apoptotic proteins post-treatment with cisplatin were examined via Western blot.An orthotopic Wilms' tumor mouse model was developed to assess the effect of miR-145 overexpression on tumor growth and cisplatin treatment response.CCK8,clonogenic formation,and Transwell assays indicated that miR-145 overexpression group exhibited reduced proliferation,migration,and invasion of Wilms' tumor cells compared to the control.Western blot results demonstrated that miR-145 overexpression suppressed EMT in Wilms' tumor by inhibiting the Smad-mediated TGF-β pathway.MiR-145 significantly induced apoptosis in these cells and improved the therapeutic response to cisplatin,diminishing drug resistance.The orthotopic Wilms' tumor mouse model validated that miR-145 inhibited primary tumor growth in the Wilms' tumor xenograft and enhanced cisplatin treatment response.Taken together,miR-145 inhibits EMT in Wilms' tumor by suppressing the Smad-mediated TGF-β pathway,effectively reducing cell proliferation,migration,and invasion.The miR-145/Smad/TGF-β/EMT axis emerges as a potential therapeutic target for Wilms' tumor.