The microRNAs miR-302d and miR-93 inhibit TGFB-mediated EMT and VEGFA secretion from ARPE-19 cells. (December 2020)

• Record Type: Journal Article
• Authors: Fuchs, Heiko R.; Meister, Roland; Lotke, Rishikesh; Framme, Carsten
• Is Part Of: Experimental eye research. Volume 201(2020)
• Publication Date: 2020-12
• Subjects: microRNA -- TGFB -- EMT -- miR-302 -- miR-93 -- PVR -- VEGFA -- AMD -- RPE -- ARPE-19; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108258
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: The transforming growth factor-beta (TGFB) plays an essential role in the pathogenesis of some ophthalmologic diseases, including neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR). TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor, which together activate several genes, including VEGFA. TGFB treated ARPE-19 cells show an increased proliferation rate and undergo epithelial to mesenchymal transition (EMT). Since microRNAs (miRNAs) are capable of inhibiting the translation of multiple genes, we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels. In this study, we focused on two miRNAs, miR-302d and miR-93, which inhibit TGFB signalling pathway and therefore TGFB-induced EMT transition as well as VEGFA secretion from ARPE-19 cells. Furthermore, we could show that both miRNAs can retransform TGFB-stimulated mesenchymal ARPE-19 cells towards the morphological epithelial-like state. Taken together, transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies. Highlights: miR-302d and miR-93 are capable of inhibiting TGFB-mediated VEGFA secretion from ARPE-19 cells by directly targeting TGFBR2, as well as VEGFA. Both miRNAs can prevent TGFB–induced EMT of ARPE-19 cells in vitro, mainly by inhibiting TGFBR2 at the transcriptional and translational level. Both miRNAs can revert TGFB-induced mesenchymal ARPE-19 cells towards an epithelial-like state and therefore promote MET.