SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway.

OBJECTIVES:Podocyte injury is a prediction marker of diabetic nephropathy (DN), and AKT/mTOR pathway-mediated inhibition of autophagy is widely reported to contribute to podocyte damage. Recent study stated that sperm-associated antigen 5 activated AKT/mTOR signalling in bladder urothelial carcinoma, indicating might regulate autophagy and play a role in podocyte damage. MATERIALS AND METHODS:Apoptosis and autophagy of human podocytes (HPCs) were detected by flow cytometry and immunofluorescence (IF). Gene level was assessed by Western blot and RT-qPCR. Molecular interactions were determined by pulldown, RNA immunoprecipitation (RIP), co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and luciferase reporter mRNA and protein levels were upregulated under high glucose treatment in HPCs. Silencing duanyu1842G5 reversed the increase of apoptosis and decrease of autophagy in high glucose-treated HPCs. Later, we found a long non-coding RNA (lncRNA) duanyu1842G5 antisense RNA1 as a neighbour gene to Mechanistically, YY1 transcriptionally upregulated and duanyu1842G5 in high glucose-treated podocytes. duanyu1842G5-AS1 acted as a competitive endogenous RNA (ceRNA) to regulate miR-769-5p/YY1 axis and induce duanyu1842G5. duanyu1842G5-AS1 interacted with ubiquitin-specific peptidase 14 (USP14) and leads to de-ubiquitination and stabilization of duanyu1842G5 protein. CONCLUSIONS:This study revealed that duanyu1842G5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via pathway, indicating as a potential target for the alleviation of podocyte injury and offering new thoughts for the treatments of DN.

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