linc00174 deteriorates the pathogenesis of diabetic retinopathy via miR-26a-5p/PTEN/Akt signalling cascade-mediated pyroptosis

Purpose: We aim to investigate the potential role and underlying mechanisms of linc00174 on Pyroptosis in the pathogenesis of DR.

Methods: Expression patterns of linc00174, miR-26a-5p and PTEN in human retinal microvascular endothelial cells (hRMECs) were detected by quantitative Real-Time PCR (qRT-PCR) and Western blot, respectively. Biological functions of linc00174 on cell proliferation and Pyroptosis were evaluated by CCK-8, flow cytometry, Caspase-1 activity assays, respectively. Luciferase reporter assay was employed to verify the interaction between miR-26a-5p and linc00174/PTEN. Streptozotocin (STZ)-induced DR in mice was further constructed to verify the potential role of linc00174 in vivo. Hematoxylin and eosin (H&E) and immunohistochemical staining were performed to assess the pathological changes and Caspase-1 expression in retinal tissues.

Results: Up-regulated linc00174 and PTEN and down-regulated miR-26a-5p were uncovered in hRMECs treated with high glucose (HG). Mechanistically, linc00174 served as a Sponge of miR-26a-5p to facilitate PTEN expression. Functionally, knockdown of linc00174 inhibited HG-induced Pyroptosis of hRMECs via targeting miR-26a-5p. Moreover, linc00174/miR-26a-5p axis participated in HG-induced Pyroptosis via PTEN/Akt signaling cascade. Further, silencing of linc00174 attenuated Pyroptosis via regulating miR-26a-5p/PETN axis in DR mice.

Conclusions: Collectively, our study reveals that linc10074 deteriorates the pathogenesis of DR via miR-26a-5p/PTEN/Akt signalling cascade, which may shed light on the discovery of potential therapeutic agents for DR treatment.