LncRNA-MEG3 alleviates high glucose induced inflammation and apoptosis of retina epithelial cells via regulating miR-34a/SIRT1 axis

Background: Diabetic retinopathy (DR) is the serious complication of diabetes, which could lead to blindness. Inflammation and apoptosis are hallmark of DR, but mechanism of their regulation is little known. LncRNA-MEG3 is associated with multiple biological processes including proliferation, apoptosis and inflammation response, and is dramatically decreased in DR. However, the role and underlying mechanism of MEG3 in DR is unclear. This study is aimed to reveal the signaling mechanisms of MEG3 in inflammation and apoptosis of DR. Methods: ARPE-19 cells were applied for this research. MEG3 was cloned into pcDNA3.1. miR-34a was over expressed and inhibited by transfecting with mimics and inhibitor, respectively. The expression level was detected by qRT-PCR and western blotting. The targeted regulatory relationship was analyzed by dual luciferase assay. Cytokine secretion, cell viability and apoptosis were detected by ELISA assay, MTT assay and flow cytometry analysis, respectively. Results: High glucose (HG) inhibited MEG3 and SIRT1 expression and enhanced miR-34a expression. MEG3 could promote SIRT1 expression by targeting miR-34a. MEG3 overexpression and miR-34a knockdown could inhibit HG-induced apoptosis and secretion of inflammation cytokines including IL-1 beta, IL-6 and TNF-alpha, but miR-34a overexpression alleviated such effects of MEG3. Furthermore, MEG3 overexpression also inhibited NF-kappa B signaling pathway and increased Bcl-2/Bax ratio via down-regulating miR-34a. Conclusion: MEG3 could alleviate HG-inducing apoptosis and inflammation via inhibiting NF-kappa B signaling pathway by targeting miR-34a/SIRT1 axis. This finding illustrated the function and mechanism of MEG3 in DR, and MEG3 might serve as potential therapeutic target for DR.