A Circular RNA Binds To and Activates AKT Phosphorylation and Nuclear Localization Reducing Apoptosis and Enhancing Cardiac Repair

作者：Zeng, Yan; Du, William W.; Wu, Yingya; Yang, Zhenguo; Awan, Faryal Mehwish; Li, Xiangmin; Yang, Weining; Zhang, Chao; Yang, Qi; Yee, Albert; Chen, Yu; Yang, Fenghua; Sun, Huan; Huang, Ren; Yee, Albert J.; Li, Ren-Ke; Wu, Zhongkai; Backx, Peter H.; Yang, Burton B.^*

来源：Theranostics, 2017, 7(16): 3842-3855.

DOI：10.7150/thno.19764

• circ-Amotl1
• AKT
• PDK
• apoptosis
• heart repair

As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1-and AKT1-binding sites were then identified in silico. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.

• 出版日期2017
• 单位中南大学; 广东省微生物研究所; 广东省实验动物监测所; 河北医科大学; 中山大学