miR-21 promotes bevacizumab induced epithelial-mesenchymal transition in retinal pigment epithelial cells by regulating Snail expression via TGFβ1/smad2/3 signaling pathway

Background The purpose of this study was to investigate the role of microRNA-21 (miR-21) on bevacizumab (BEV)-induced Epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells in vitro. Methods Human retinal pigment epithelial cells line (ARPE-19) were exposed to clinical dosage of BEV and miR-21 expression was measured by qRT-PCR assay. The effects of miR-21 on BEV-induced EMT were examined through gain- or loss- expression of miR-21 using miR-21 mimic or inhibitor. The expression of α-smooth muscle actin (α-SMA), E-cadherin, Snail, TGFβ1 and smad2/3 were detected by western blot. TGFβ1/smad2/3 signaling was inhibited by using SB431542 and SIS3. Results Clinical dosage of BEV caused EMT and enhanced miR-21 expression in ARPE-19 cells. The inhibition of miR-21 attenuated the EMT effect of BEV, while over-expression of miR-21 promoted this activity. Snail was up-regulated by BEV and the promotion was partially suppressed by miR-21 inhibitor and aggravated by miR-21 mimic. miR-21 regulated BEV-induced TGFβ1 increasing and smad2/3 phosphorylation. The EMT and Snail expression promoted by BEV and miR-21 mimic in ARPE-19 cells was impaired by inhibition of TGFβ1/smad2/3 signaling. Conclusions miR-21 promoted BEV-induced EMT in ARPE cells through up-regulating of Snail expression via regulation of TGFβ1/smad2/3 signaling pathway. miR-21 might be a potential miRNA-based therapeutic target in reducing BEV-induced subretinal fibrosis.