Diabetic 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.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81970786 and 81670836), the Medical Science and Technology Project Jointly Built of Henan Province (Grant No. LHGJ20190196), and the Key Scientific Research Projects of Henan Colleges and Universities (Grant No. 20A320031).
The authors declare no competing interests.
The procedures involved in humen were carefully carried out in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University Committee.
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Li, X., Sun, M., Cheng, A. et al. LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis. Lab Invest 102, 452–460 (2022). https://doi.org/10.1038/s41374-021-00713-3