Research Paper Volume 13, Issue 13 pp 17155—17176
Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis
- 1 Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
- 2 School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
- 3 School of Clinical Medicine, Ningxia Medical University, Ningxia 750004, China
Received: November 18, 2020 Accepted: March 14, 2021 Published: June 3, 2021https://doi.org/10.18632/aging.203062
How to Cite
Copyright: © 2021 Zhu 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.
Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.