Long non-coding RNA HOXA11-AS protects the barrier function of corneal endothelial cells by sponging microRNA-155 to alleviate corneal endothelial injury.

ABSTRACT

OBJECTIVES: Corneal endothelial cells (CECs) are extremely vulnerable to injury. In this study, the role and mechanism of action of the long non-coding RNA HOXA11-AS during corneal endothelial injury (CEI) were evaluated in vivo and in vitro. METHODS: Scratch wounds were made to induce CEI in the corneal endothelium of rats and mice. Homeobox A11 (HOXA11)-AS expression was determined at different time points using quantitative real-time PCR. Human CECs with HOXA11-AS overexpression or downregulation were examined for survival, ferroptosis, and migration. Bioinformatics and dual-luciferase reporter assays were used to investigate the correlation between HOXA11-AS and microRNA (miR)-155. RESULTS: HOXA11-AS expression was reduced in the corneal endothelium in a time-dependent manner. Scratch wounds triggered high rates of ferroptosis and migration in CECs and impaired cell proliferation. HOXA11-AS overexpression partially attenuated the scratch wound-induced changes in proliferation, ferroptosis, and migration, whereas silencing HOXA11-AS had the opposite effects. Moreover, HOXA11-AS served as a competing endogenous RNA of miR-155. Levels of miR-155 were upregulated in the corneal endothelium following the scratch injury, and this upregulation abolished the effect of HOXA11-AS overexpression on the behavior of CECs after injury; miR-155 inhibition counteracted the effect of HOXA11-AS silencing. CONCLUSIONS: HOXA11-AS exerts protective effects against CEI by sponging miR-155, suggesting that these loci are treatment targets for corneal endothelial disorders.