Research Paper Volume 12, Issue 3 pp 3010—3024

microRNA-1203 targets and silences cyclophilin D to protect human endometrial cells from oxygen and glucose deprivation-re-oxygenation

Hong-Bin Xu1,2, *, , Yu-Fan Zheng3, *, , Di Wu3, *, , Ya Li4, *, , Li-Na Zhou5, , You-Guo Chen1, ,

  • 1 Obstetrics and Gynecology Department, The First Affiliated Hospital of Soochow University, Suzhou, China
  • 2 Obstetrics and Gynecology Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
  • 3 Institute of Neuroscience, Soochow University, Suzhou, China
  • 4 The Central Lab, North District, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, China
  • 5 Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China
* Equal contribution

Received: October 20, 2019       Accepted: January 12, 2020       Published: February 10, 2020
How to Cite

Copyright: © 2020 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) stimulation to the human endometrial cells mimics ischemia-reperfusion injury. Cyclophilin D (CypD)-dependent programmed necrosis pathway mediates OGDR-induced cytotoxicity to human endometrial cells. We here identified a novel CypD-targeting miRNA, microRNA-1203 (miR-1203). In T-HESC and primary human endometrial cells, ectopic overexpression of miR-1203, using a lentiviral construct, potently downregulated the CypD 3’-untranslated region (3’-UTR) activity and its expression. Both were however upregulated in endometrial cells with forced miR-1203 inhibition by its anti-sense sequence. Functional studies demonstrated that ectopic miR-1203 overexpression in endometrial cells alleviated OGDR-induced programmed necrosis, inhibiting mitochondrial CypD-p53-adenine nucleotide translocator 1 association, mitochondrial depolarization, reactive oxygen species production, and medium lactate dehydrogenase release. Contrarily OGDR-induced programmed necrosis and cytotoxicity were intensified with forced miR-1203 inhibition in endometrial cells. Significantly, ectopic miR-1203 overexpression or inhibition failed to change OGDR-induced cytotoxicity in CypD-knockout T-HESC cells. Furthermore, ectopic miR-1203 overexpression was unable to protect T-HESC endometrial cells from OGDR when CypD was restored by an UTR-depleted CypD construct. Collectively, these results show that miR-1203 targets and silences CypD to protect human endometrial cells from OGDR


3′-UTR: 3′-untranslated region; ANT1: adenine nucleotide translocator type 1; CCK-8: cell Counting Kit-8; CypD: cyclosporin A; CsA: cyclophilin-D; GRh2: ginseng Rh2; KGF: keratinocyte growth factor; KO: knockout; LDH: lactate dehydrogenase; miR-1201: microRNA-1201; miR-30b: microRNA-30b; OD: optic density; OGD: oxygen glucose deprivation; OGDR: oxygen and glucose deprivation-re-oxygenation; ROS: reactive oxygen species; PVDF: polyvinylidene difluoride; qPCR: quantitative real-time PCR; shRNA: short hairpin RNA; SD: standard deviation.