LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis

Abstract

AbstractDiabetic cataract (DC) is a major ocular complication secondary to diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important event in DC progression. Long non-coding RNAs (lncRNAs) and microRNAs are involved in various biological processes and disorders. The aim of this study was to investigate the roles of lncRNA growth arrest-specific transcript 5 (GAS5) and microRNA-204-3p (miR-204-3p) deregulation in the pathogenic mechanism of high glucose (HG)-stimulated LECs. The results show that GAS5 was up-regulated, whereas miR-204-3p was down-regulated in anterior lens capsule tissues of DC patients and in HG-treated LECs compared to their controls, respectively. Functional experiments suggest that the lentivirus-mediated depletion of GAS5, as well as overexpression of miR-204-3p, suppressed migration and EMT in HG-treated LECs. Further mechanistic studies revealed that lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta (TGFBR1) has a regulatory role in the process. Collectively, we demonstrated that dysregulation of GAS5 affects lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis. The current findings may provide new insights into the molecular mechanisms of DC development.Under high-glucose conditions, LECs obtain characteristics of mesenchymal cells such as high migratory capacity and invasiveness, which is the foundational basis for DC progression. The authors demonstrated that lncRNA GAS5 facilitates high glucose-induced lens epithelial cell migration and epithelial-to-mesenchymal transition by regulating the miR-204-3p/TGFBR1 axis. This study, therefore, provides novel insights into the pathogenesis of DCs.