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

Abstract

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 CoCl2 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 CoCl2 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.

β‐Amyrin ameliorates diabetic nephropathy in mice and regulates the miR‐181b‐5p/HMGB2 axis in high glucose‐stimulated HK‐2 cells

“…MiR‐92d‐3p suppresses renal fibrosis and inflammation of HG‐stimulated HK‐2 cells by inhibiting the C3/HMGB1/TGF‐β1 pathway during DN progression 52 . Long noncoding RNA maternally expressed 3 (MEG3) exacerbates the hypoxia/reoxygenation‐stimulated HK‐2 cell apoptosis via the miR‐129‐5p/HMGB1 axis 53 . In this study, HMGB2 was found to be overexpressed in HG‐stimulated HK‐2 cells and in renal tissues of STZ‐induced diabetic mice, suggesting that HMGB2 may be implicated in DN development.…”

Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma

“…At the outer mitochondrial membrane, the MCL-1 isoform antagonizes apoptosis like other anti-apoptotic BCL-2 molecules, whereas the amino-terminal isoform of MCL-1 imported into the mitochondrial matrix promotes normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure and oligomeric ATP synthase activity 66 . LncRNA MEG3(maternally expressed gene 3), a tumor suppressor, has been shown to be involved in the development of cancer 67 - 68 . And Gong A et al found that IncRNA MEG3 mediates ST3Gal1 to regulate EGFR phosphorylation, which will downregulate Bcl-2 and prcaspase-2 expression,upregulate caspase-2 and cytochrome c release 69 , leading to mitochondrial dysfunction and inducing apoptosis in ccRCC cells.…”

Non-Coding RNAs in Kidney Diseases: The Long and Short of Them

“…In two recent studies, HK2 cells under hypoxia increased HIF-1α levels through the LncRNA PRINS and its interaction with CCL5 [ 58 ]. The LncRNA MEG3 was also found to be elevated in human tubuloepithelial cells, aggravating hypoxia/reoxygenation induced apoptosis throughout regulation of the miR-129-5p/HMGB1 axis [ 59 ]. All these results confirm the emerging role of LncRNAs in the pathophysiology of I/R renal injury and their possible use as biomarkers in this pathological setting.…”