LINK-A lncRNA activates HIF1[alpha] signaling and inhibits podocyte cell apoptosis in diabetic nephropathy

Previous studies have revealed that long intergenic non-coding RNA for kinase activation (LINK-A), a long non-coding RNA (lncRNA) promotes disease progression in triple-negative breast cancer by activating hypoxia-inducible factor 1[alpha] (HIF1[alpha]). However, the activation of HIF1[alpha] has also been demonstrated to improve diabetic nephropathy. It is therefore reasonable to expect that LINK-A may also participate in diabetic nephropathy. In the current study, the expression of LINK-A lncRNA and HIF1[alpha] was determined in renal biopsies of patients with diabetic nephropathy. LINK-A lncRNA and HIF1[alpha] expression levels were detected by reverse transcription quantitative (RT-q) PCR and ELISA in diabetic patients without complications and used as controls. Correlations between LINK-A lncRNA and HIF1[alpha] expression were analyzed using Pearson's correlation coefficient. Effects of lncRNA and HIF1[alpha] overexpression on LINK-A lncRNA expression, HIF1[alpha] expression and cell apoptosis were assessed using RT-qPCR, western blotting and a cell apoptosis assay. The results revealed that LINK-A lncRNA and HIF1[alpha] were downregulated in patients with diabetic nephropathy, as well as in diabetic patients without complications. The lowest expression of LINK-A lncRNA and HIF1[alpha] were observed in healthy controls. A positive correlation was identified between LINK-A lncRNA and HIF1[alpha] in both patients groups, but not in the control group. LINK-A lncRNA and HIF1[alpha] overexpression inhibited the apoptosis of mouse podocyte cells under a high glucose treatment. LINK-A lncRNA overexpression also promoted HIF1[alpha] expression in mouse podocyte cells, while HIF1[alpha] overexpression did not significantly affect LINK-A lncRNA expression. In conclusion, LINK-A lncRNA may activate HIF1[alpha] signaling resulting in the improvement of diabetic nephropathy treatment. Key words: diabetic nephropathy, long non-coding RNA, long intergenic non-coding RNA for kinase activation, hypoxia-inducible factor 1[alpha], mouse podocyte cells, apoptosis