Long non-coding RNA MEG3 mediates high glucose-induced endothelial cell dysfunction.

Long noncoding RNAs (lncRNAs) are implicated in the progression of diabetes mellitus (DM) and diabetes-induced endothelial dysfunction. Maternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to function as a tumor suppressor. Therefore, the aim of the present study was to investigate whether MEG3 is a potential regulator and molecular biomarker of high glucose-induced endothelial dysfunction. LncRNA Meg3-specific small interfering RNA (siRNA) and scrambled (Scr) siRNA were transfected for MEG3 dysfunction studies. RNA and protein expression were examined by quantitative RT-PCR (qPCR) and Western blot, respectively. The percentage of apoptotic cells was measured by flow cytometry. Cell viability was determined through MTT assay. This study demonstrates involvement of lncRNA MEG3 in high glucose-induced endothelial dysfunction. MEG3 is significantly downregulated in an endothelial cell model of hyperglycemia. In addition, MEG3 knockdown could exacerbate inflammatory damage in endothelial cells. Interestingly, MEG3 knockdown in HUVECs significantly induced proliferation and inhibited apoptosis by upregulating Bcl-2 and downregulating Bax, caspase-3, and P53. It should be noted that MEG3 knockdown could activate the TGF-β signaling pathway via upregulating TGF-β1, SMAD2, and SMAD7 and activate the Wnt/β-catenin signaling pathway via upregulating β-catenin and Cyclin D1 and downregulating TCF7L2. Our results indicate that MEG3 can be regarded as a novel therapeutic target and molecular biomarker for high glucose-induced endothelial dysfunction.