文献类型：期刊文献

英文题名：Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis

作者：Zhu, Zi-Jiang[1];Pang, Yao[1];Jin, Gang[1];Zhang, Hong-Yi[1];Wang, Wen-Hao[1];Liu, Jia-Wei[1];Tuo, Guang-Xin[2];Wu, Peng[2];Yang, Yi[2];Wang, Ze-Quan[3];Wang, Kui[3]

第一作者：Zhu, Zi-Jiang

通信作者：Zhu, ZJ[1]

机构：[1]Gansu Prov Peoples Hosp, Dept Thorac Surg 2, Lanzhou 730000, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Sch Clin Med, Lanzhou 730000, Peoples R China;[3]Ningxia Med Univ, Sch Clin Med, Yinchuan 750004, Ningxia, Peoples R China

第一机构：Gansu Prov Peoples Hosp, Dept Thorac Surg 2, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Peoples Hosp, Dept Thorac Surg 2, Lanzhou 730000, Peoples R China.

年份：2021

卷号：13

期号：13

起止页码：17155

外文期刊名：AGING-US

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000677491700016)】；

基金：This work was supported by National Nature Science Foundation of China (31760259) .

语种：英文

外文关键词：hypoxia; chemoresistance; esophageal cancer; EMS; miR-758-3p

摘要：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.