GSE227618 MicroRNA-494 augments fibroproliferation in human retinal pigment epithelial cells and targets p27 with cell-type specificity

Contributors : Theodore Leng ; Georgia Kamboj ; Creed StarySeries Type : Non-coding RNA profiling by arrayOrganism : Homo sapiensEpiretinal membranes (ERMs) are the result of fibro-cellular proliferation that cause distortion and impairment of central vision. We hypothesized that select microRNAs (miRs) regulate retinal fibroproliferation and ERM formation. Following IRB approval, a pilot study was performed in patients presenting for retina surgery with and without clinical ERMs. Total RNA was isolated from ERM tissue and controls from non-ERM vitreous and subjected to miR profiling via microarray analysis. MiR-494 was identified as the only miR selectively expressed at significantly greater levels, and in silico analysis identified p27 as a putative fibroproliferative gene target of miR-494. In vitro testing of miR-494 and p27 in fibroproliferation was assessed in spontaneously immortalized human retinal pigment epithelial (RPE) and human M üller cell lines, stimulated to transform into a fibroproliferative state via transforming growth factor beta (TGFb). Fibroproliferative transformation was characterized by de novo cellular expression of alpha smooth muscle actin (aSMA). In both RPE and Müller cells, both TGFb and miR-494 mimic de creased p27 expression. In parallel experiments, transfection with p27 siRNA augmented TGFb-induced aSMA expression, while only in RPE cells did co-transfection with miR-494 inhibitor decrease aSMA levels. These results demonstrate that mi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Homo sapiens Source Type: research