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

Jun Xu, Yujie Deng, Yi Wang, Xiaofang Sun, Shuqin Chen, Guoxiang Fu

Cell proliferation 2020 Feb

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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 (SPAG5) activated AKT/mTOR signalling in bladder urothelial carcinoma, indicating SPAG5 might regulate autophagy and play a role in podocyte damage. 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 assays. SPAG5 mRNA and protein levels were upregulated under high glucose treatment in HPCs. Silencing SPAG5 reversed the increase of apoptosis and decrease of autophagy in high glucose-treated HPCs. Later, we found a long non-coding RNA (lncRNA) SPAG5 antisense RNA1 (SPAG5-AS1) as a neighbour gene to SPAG5. Mechanistically, YY1 transcriptionally upregulated SPAG5-AS1 and SPAG5 in high glucose-treated podocytes. SPAG5-AS1 acted as a competitive endogenous RNA (ceRNA) to regulate miR-769-5p/YY1 axis and induce SPAG5. SPAG5-AS1 interacted with ubiquitin-specific peptidase 14 (USP14) and leads to de-ubiquitination and stabilization of SPAG5 protein. This study revealed that SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway, indicating SPAG5-AS1/SPAG5 as a potential target for the alleviation of podocyte injury and offering new thoughts for the treatments of DN. © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

Citation

Jun Xu, Yujie Deng, Yi Wang, Xiaofang Sun, Shuqin Chen, Guoxiang Fu. SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. Cell proliferation. 2020 Feb;53(2):e12738