Background: To explore the role and possible mechanism of miR-21 in anti-VEGF drug-induced epithelial-mesenchymal transformation (EMT) in human retinal pigment epithelium (ARPE-19) cells, and to seek more therapeutic targets to improve prognosis vision.
Methods: ARPE-19 cells were exposed to clinical dosage of bevacizumab and miR-21 expression was measured by real-time polymerase chain reaction (RT-PCR) assay. MiR-21 mimic and inhibitor were transfected into bevacizumab-induced ARPE-19, the expression of α-smooth muscle actin (α-SMA), E-cadherin , and SNAI1 were detected by cell immunofluorescence and Western blotting.
Results: Clinical dosage of bevacizumab caused EMT and enhanced miR-21 expression in ARPE-19 cells (P< 0.05). The inhibition of miR-21 attenuated the EMT effect of bevacizumab, while overexpression of miR-21 promoted this activity (P< 0.05). The SNAI1 was up-regulated by bevacizumab and promotion was partially suppressed by the miR-21 inhibitor and aggravated by the miR-21 mimic (P< 0.05).
Conclusion: MiR-21 promotes bevacizumab-induced EMT in ARPE cells which is significantly positively correlated with SNAI1. MiR-21 might be a potential miRNA-based therapeutic target for reducing bevacizumab-induced subretinal fibrosis.
Keywords: bevacizumab, epithelial-mesenchymal transition, MiR-21 , SNAI1 , therapeutic target