Long non-coding RNA RPSAP52 upregulates Timp3 by serving as the endogenous sponge of microRNA-365 in diabetic retinopathy.

Diabetic retinopathy (DR) is a serious complication of diabetes and the most common metabolic disorder. Recently, long non-coding (lnc)RNAs have been identified as critical regulators of DR. Ribosomal protein SA pseudogene 52 (RPSAP52) is an oncogenic lncRNA expressed in pituitary tumors. The present study aimed to investigate the functions of RPSAP52 in DR. RPSAP52 levels in the plasma of diabetic patients with or without DR complication was detected. Luciferase reporter assays, RT-qPCR and western blotting were performed to detect the interaction between RPSAP52 and micro RNA (miR)-365. Moreover, expression vectors of RPSAP52 and Timp3, as well as miR-365 mimics were transfected into ARPE-19 cells exposed to high glucose and the apoptotic cells were detected. The results showed that RPSAP52 was downregulated in patients with DR compared with patients with diabetes without obvious complications. RPSAP52 directly interacted with miR-365, while overexpression of RPSAP52 and miR-365 did not affect the expression of one another. In addition, overexpression of RPSAP52 upregulated TIMP metallopeptidase inhibitor 3 (Timp3) in retinal pigment epithelial (RPE) cells. High glucose treatment led to downregulated RPSAP52 and Timp3, but upregulated miR-365 in RPE cells. Moreover, cell apoptosis analysis identified that overexpression of RPSAP52 and Timp3 led to a decreased apoptotic rate of RPE cells under high glucose treatment. Therefore, it was speculated that RPSAP52 may upregulate Timp3 by serving as the endogenous sponge of miR-365 in DR to suppress RPE cell apoptosis.