MEG3 aggravates hypoxia/reoxygenation induced apoptosis of renal tubular epithelial cells via the miR-129-5p/HMGB1 axis.

The apoptosis of renal tubular epithelial cells (TECs) during ischemia/reperfusion (I/R) facilitates the progression of acute kidney injury (AKI). This study aimed to probe the role of long noncoding RNA maternally expressed 3 (MEG3) in I/R-induced apoptosis of TECs. In this study, with CoCl and hypoxia/reoxygenation treatments, cell models were established to mimic I/R using the human kidney tubular cell line HK-2. In HK-2 cells, expression of MEG3 detected using quantitative real-time polymerase chain reaction (qRT-PCR), was significantly upregulated after CoCl treatment and hypoxia/reoxygenation treatment. The results of cell counting kit-8 assay and flow cytometry suggested that knockdown of MEG3 significantly increased the viability of HK-2 cells but inhibited its apoptosis, while overexpression of MEG3 exerted the reverse effects. Additionally, expression levels of interleukin 6 and tumor necrosis factor-α in the medium were elevated after MEG3 was overexpressed in HK-2 cells. Together with qRT-PCR and Western blot analysis, a dual-luciferase reporter gene assay was used to verify the interactions among MEG3, miR-129-5p, and HMGB1. The results demonstrated that in HK-2 cells, miR-129-5p was a target of MEG3, and HMGB1 served as a target gene of miR-129-5p. Besides this, compared with the control group, the expression levels of MEG3 and HMGB1 in samples derived from AKI patients were remarkably upregulated, and the expression of miR-129-5p was downregulated. Therefore, taken together, we conclude that the overexpression of MEG3 induced by I/R promotes apoptosis of TECs via regulating the miR-129-5p/HMGB1 axis.