Clinical Ophthalmology (Oct 2023)
MiR-21 Participates in Anti-VEGF-Induced Epithelial Mesenchymal Transformation in RPE Cells
Abstract
Xianghui Hao,1 Yingbin Hua,1 Chaohui Xie,1 Haifeng Xu1,2 1State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China; 2Qingdao Eye Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, People’s Republic of ChinaCorrespondence: Haifeng Xu, Qingdao Eye Hospital, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 5 Yanerdao Road, Qingdao, Shandong, 266071, People’s Republic of China, Email [email protected]: 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.Graphical Abstract: Keywords: bevacizumab, epithelial-mesenchymal transition, MiR-21, SNAI1, therapeutic target
