Exosomal miR-4488 and miR-1273g-5p inhibit the epithelial-mesenchymal transition of transforming growth factor β2-mediated retinal pigment epithelial cells by targeting ATP-binding cassette A4

Exosomal microRNAs (miRNAs) have been shown to be involved in the regulation of many disease progression, including proliferative vitreoretinopathy (PVR). However, the roles of exosomal miR-4488 and miR-1273 g-5p in PVR progression have not been demonstrated. Transforming growth factor beta 2 (TGF-beta 2)-induced ARPE-19 cells were used to stimulate the epithelial-mesenchymal transition (EMT) of cells. Exosomes derived from TGF-beta 2-induced ARPE-19 cells were identified by transmission electron microscopy and nanoparticle tracking analysis. The expression levels of miR-4488, miR-1273 g-5p and ATP-binding cassette A4 (ABCA4) were measured by quantitative real-time PCR. The promotion levels of exosomes markers, EMT markers, apoptosis markers and ABCA4 were determined by western blot analysis. The migration, invasion and apoptosis of cells were determined by transwell assay, wound healing assay and flow cytometry. Our data showed that miR-4488 and miR-1273 g-5p were lowly expressed in TGF-beta 2-induced ARPE-19 cells. Overexpressed exosomal miR-4488 and miR-1273 g-5p could inhibit the EMT, migration, invasion, and promote apoptosis in TGF-beta 2-induced ARPE-19 cells. In addition, ABCA4 was a target of miR-4488 and miR-1273 g-5p. Overexpressed ABCA4 also could reverse the negatively regulation of exosomal miR-4488 and miR-1273 g-5p on the EMT, migration, and invasion of TGF-beta 2-induced ARPE-19 cells. In conclusion, our data showed that exosomal miR-4488 and miR-1273 g-5p could inhibit TGF-beta 2-stimulated EMT in ARPE-19 cells through targeting ABCA4.

Automated summary

Our findings demonstrate that exosomal miR-4488 and miR-1273 g-5p can inhibit TGF-beta 2-induced EMT in ARPE-19 cells by targeting ABCA4. Overexpression of these miRNAs suppresses migration and invasion, while promoting apoptosis in the TGF-beta 2-induced ARPE-19 cells. ABCA4 serves as a target for miR-4488 and miR-1273 g-5p, and overexpressing ABCA4 can reverse the negative regulation of the exosomal miRNAs on EMT, migration, and invasion in these cells.