TY - JOUR ID - 250662 TI - Endoplasmic Reticulum Stress Induces miR-706, A Pro-Cell Death microRNA, in A Protein Kinase RNA-Like ER Kinase (PERK) and Activating Transcription Factor 4 (ATF4) Dependent Manner JO - Cell Journal (Yakhteh) JA - CELLJ LA - en SN - 2228-5806 AU - Wang, Xiu AU - Han, Yi AU - Hu, Guodong AU - Guo, Jianbo AU - Chen, Hongyu AD - Department of Anesthesiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China AD - The Second Department of Urology, Shenyang Red Cross Hospital, Shenyang, People’s Republic of China (CHN) AD - The Third Department of General Surgery, The Fourth affiliated Hospital of China, Medical University, Shenyang, Liaoning, China Y1 - 2019 PY - 2019 VL - 22 IS - 3 SP - 394 EP - 400 KW - Activating Transcription Factor 4 KW - Caspase Activity and Apoptosis Inhibitor 1 KW - Endoplasmic Reticulum Stress KW - MiR KW - 706 KW - Protein Kinase RNA KW - Like ER Kinase DO - 10.22074/cellj.2020.6873 N2 - ObjectiveEndoplasmic reticulum (ER) stress causes an adaptive response initiated by protein kinase RNA-like ER kinase (PERK), Ire1 and ATF6. It has been reported that these upstream regulators induce microRNAs. The current study was designed to find a novel microRNA that mediates ER stress components and finally contributes to cell fate decision. Materials and Methods In this experimental study, miR-706 levels were checked under different conditions of ER stress induced by Thapsigargin, Tunicamycin or low glucose media. PERK and ATF4 were knocked-down by administration of lentivirus-mediated short hairpin RNA to explore the effect of ER stress related proteins on miR-706 expression. The effect of miR-706 on caspase activity and apoptosis inhibitor 1 (CAAP1) levels were examined by using mimic-miR-706. The role of CAAP1 in inhibiting cell death (measured by Annexin V staining) and contributing to patient overall survival (measured by Kaplan-Meier estimate) were further confirmed by anti- miR-706 and CAAP1 knock-down. Results We showed that Thapsigargin or Tunicamycin triggered ER stress leading to the induction of miR-706. miR-706 induction is dependent on PERK and its downstream regulator ATF4, as knocking-down of PERK and ATF4 suppressed miR-706 induction in response to ER stress. Knocking-down of miR-706 reduces cell death triggered by ER stress, indicating that miR-706 is pro-cell death microRNA. We further identified CAAP1 as a miR-706 target in regulating ER stress initiated cell death. Conclusion Collectively, our results pointed to an ER signaling network consisting of proteins, microRNA and novel target. UR - https://www.celljournal.org/article_250662.html L1 - https://www.celljournal.org/article_250662_e10c77735ce860102e52c1d4fc14fac5.pdf ER -