Research Paper Volume 13, Issue 3 pp 4663—4673

Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis

Peng Wu1, , Chunxiang Li2,3, , Dong mei Ye4, , Kenan Yu5, , Yuxuan Li4, , Hailin Tang4, , Gaoshen Xu2,3, , Shuijing Yi5, , Zhiwei Zhang1,2,3,4, ,

  • 1 Department of Critical Care Medicine, Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China
  • 2 Yueyang Maternal and Child Health Hospital, Yueyang 414000, Hunan Province, China
  • 3 Innovative Practice Base for Postgraduate Training of Basic Medicine and Clinical Collaboration, University of South China and Yueyang Maternal and Child Health Hospital, Yueyang 414000, Hunan Province, China
  • 4 Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute of Hengyang Medical College, University of South China, Hengyang 421001, Hunan Province, China
  • 5 Department of Gynecology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China

Received: July 8, 2020       Accepted: December 25, 2020       Published: February 2, 2021
How to Cite

Copyright: © 2021 Wu 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.


Background: Circular RNAs (circRNAs) is one kind of non-coding RNAs (ncRNAs) and exert crucial functions in biological processes and intracellular gene expression modulation. However, the biological roles and expression status of the majority of circRNAs still remain unknown in cervical cancer.

Results: In this study, circEPSTI1 (hsa_circRNA_000479) was significantly upregulated in cervical cancer. We first discovered the impact of circRNA on cell ferroptosis in cervical cancer. Interestingly, circEPSTI1 attenuates the effect of ferritin which is mediated by SLC7A11 based on lipid peroxidation measurements and reduced glutathione and glutathione (GSH/GSSG) assay.

Conclusions: circEPSTI1-miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. Our findings provided experimental evidences which revealed that circEPSTI1 might act as a new and useful biomarker for monitoring and treatment target for cervical cancer.

Methods: The expression of circEPSTI1 was examined in cervical cancer cells. Then, we observed the impact of circEPSTI1 expression on the proliferation of cervical cancer by loss-of-function assays both in vivo and vitro. RIP and luciferase reporter assay revealed that circEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. We applied mouse xenograft experiments in mice to validate our results.


circRNAs: Circular RNAs; IARC: International Agency for Research on Cancer; miRNA: microRNA; ROS: reactive oxygen species; GPX4: glutathione peroxidase 4; SLC3A2: solute carrier family 3 membrane 2; SLC7A11: solute carrier family 7 membrane 11; SD: standard deviation.