RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration.

Zhenxuan Shao, Libin Ni, Sunli Hu, Tianzhen Xu, Zaher Meftah, Zupo Yu, Naifeng Tian, Yaosen Wu, Liaojun Sun, Aimin Wu, Zongyou Pan, Linwei Chen, Weiyang Gao, Yifei Zhou, Xiaolei Zhang, Xiangyang Wang

Cell proliferation 2021 Feb

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Diabetes is a risk factor for intervertebral disc degeneration (IVDD). Studies have demonstrated that diabetes may affect IVDD through transcriptional regulation; however, whether post-transcriptional regulation is involved in diabetic IVDD (DB-IVDD) is still unknown. This study was performed to illustrate the role of HuR, an RNA-binding protein, in DB-IVDD development and its mechanism. The expression of HuR was evaluated in nucleus pulposus (NP) tissues from diabetic IVDD patients and in high glucose-treated NP cells. Senescence and autophagy were assessed in HuR over-expressing and downregulation NP cells. The mRNAs that were regulated by HuR were screened, and immunoprecipitation was applied to confirm the regulation of HuR on targeted mRNAs. The results showed that the expression of HuR was decreased in diabetic NP tissues and high glucose-treated NP cells. Downregulation of HuR may lead to increased senescence in high glucose-treated NP cells, while autophagy activation attenuates senescence in HuR deficient NP cells. Mechanistic study showed that HuR prompted Atg7 mRNA stability via binding to the AU-rich elements. Furthermore, overexpression of Atg7, but not HuR, may ameliorate DB-IVDD in rats in vivo. In conclusion, HuR may suppress senescence through autophagy activation via stabilizing Atg7 in diabetic NP cells; while Atg7, but not HuR, may serve as a potential therapeutic target for DB-IVDD. © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

Citation

Zhenxuan Shao, Libin Ni, Sunli Hu, Tianzhen Xu, Zaher Meftah, Zupo Yu, Naifeng Tian, Yaosen Wu, Liaojun Sun, Aimin Wu, Zongyou Pan, Linwei Chen, Weiyang Gao, Yifei Zhou, Xiaolei Zhang, Xiangyang Wang. RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration. Cell proliferation. 2021 Feb;54(2):e12975