Fig. 5

Increased matrix stiffness enhances TGF β1 autocrine and triggers EMT in HCC cells. a The expression of TGFβ1 in HCC cells under different stiffness stimulation. L, low-stiffness substrate, 6 KPa; M, medium-stiffness substrate, 10 KPa; H, high-stiffness substrate, 16 KPa. b TGFβ1 expression in orthotopic HCC tumors in group N, group M, and group H. N, normal stiffness; M, medium stiffness; H, high stiffness. Scale bar, 1000 μm. c miRNA-24-3p expression in HCC cells grown on different stiffness substrates. d Expression of Furin in HCC cells grown on different stiffness substrates. e Dual luciferase assay validated a specific regulation of miRNA-24-3p on Furin 3′UTR. f Expressions of Furin, TGFβ1, Smad2/3, p-Smad2, p-Smad3, HMGA2, and Snail in LV-miRNA-24-3p-overexpression-transfected HCC cells grown on high stiffness substrate (16 KPa). g Expressions of Furin, TGFβ1, Smad2/3, p-Smad2, p-Smad3, HMGA2, and Snail in LV-miRNA-24-3p-interference-transfected HCC cells grown on low stiffness substrate (6 KPa). h Suppression of integrin β1 resulted in an increase of miRNA-24-3p in HCC cells grown on high stiffness substrate (16 KPa). i Knockdown of integrin β1 suppressed the expressions of Furin, TGFβ1, Smad2/3, p-Smad2, and p-Smad3 in HCC cells grown on high stiffness substrate (16 KPa). j Inhibition of miRNA-24-3p reversed the expressions of Furin, TGFβ1, Smad2/3, p-Smad2, p-Smad3, HMGA2, and Snail in transfected HCC cells with LV-shRNA-ITGβ1 under higher stiffness stimulation. Error bars indicate SD. LV-OE-miR-24-3p, miRNA-24-3p-overexpression; LV-shRNA-miR-24-3p, miRNA-24-3p inhibition; *P < 0.05, **P < 0.01, ***P < 0.001