Fig. 6: Metformin attenuated the activity of TGF-β signaling via downregulating INHBA.

a GSEA analyzed INHBA positive-associated gene sets in the GSE15781 dataset. b Prediction of proteins interacting with INHBA by STRING database. c The correlation of INHBA and TGF-B1 in CRC tissues. Data from GEPIA database. d, e Knocking down (d), or overexpressing (e) INHBA decreased or increased the activity of TGF-β pathway. f Metformin treatment reduced the phosphorylation level of Smad2 in various CRC cells. g Exogenous expressing INHBA partly rescued the inhibition effect of metformin on the activity of TGF-β/smad signaling. h, i A represent image of IHC showing metformin treatment inactivated TGF-β signaling in CRC tissues (h) and subcutaneous tumors (i). Magnification: 100× (low); 40× (up). Scale bar: 100 µm (low); 400 µm (up). The values are shown as the mean ± SD and experiments were independently repeated three times. *P < 0.05, ***P < 0.001.