Fig. 6: MAGI3 inhibits MAS-induced ccRCC tumor proliferation in vivo.
A–C Upregulation of MAGI3 inhibits MAS-induced tumor growth in xenografted ccRCC cells in BLAB/c nude mice. After subcutaneously implanting 786-O cells overexpressing MAGI3 or control vector cells, subcutaneous injections of 0.5 mg/kg Ang-(1-7) were administered every 24 h upon tumor formation. Tumor volumes were monitored at specified intervals, with the largest tumors allowed to reach 1000 mm3. Upon sacrifice, tumor weights were recorded. Displayed are representative images of xenograft tumors (A) tumor weight (B) and tumor growth curves (C). D, E Downregulation of pERK and Ki-67 levels in transplanted tumors with MAGI3 overexpression. Paraffin sections from the 786-O ccRCC tumors in nude mice were subjected to immunohistochemistry staining, utilizing MAGI3, pERK, and Ki-67 antibodies. Scale bars: 50 μm. Data are presented as mean ± SEM. Significance levels are indicated as *, **, *** (P < 0.05, P < 0.01, P < 0.001). F Representative immunohistochemistry staining of MAGI3 and pERK in kidney tissues from Magi3−/− or Magi3+/+ mice. Scale bars: 200 μm. Right panels exhibit magnifications of the dashed areas on the left. Scale bars: 50 μm. G Magi3 knockdown fails to trigger ERK phosphorylation by blocking MAS activation with A779. Western blot analysis of pERK in kidney tissues from Magi3−/− or Magi3+/+ mice, with or without A779 pretreatment. H MAGI3’s impact on ccRCC cell proliferation mediated by the MAS/ERK axis. Enrichment plots from gene set enrichment analysis (GSEA) reveal significant activation of MAS, ERK, cell cycle, and proliferation pathways in ccRCC specimens with middle-low (M/L, <261.5 RPKM) MAGI3 expression from the TCGA ccRCC patients with stage I.
