• Panpan Zhan, Xiong Shu, Meng Chen, Lixin Sun, Long Yu, Jun Liu, Lichao Sun, Zhihua Yang, and Yuliang Ran.
• State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China.
• Life Sci. 2021 Jul 1; 276: 119405.

AimsGastric cancer stem cells (GCSCs) have been used as a therapeutic target. This study aims to estimate the role of miR-98-5p (termed miR-98) in the development of GCSCs.Main MethodsThe expression of miR-98 in CD44+ GCSCs was verified by RT-PCR. The miR-98 was overexpressed in CD44+ GCSCs by Lentivirus. The ability of self-renewal, invasion, chemoresistance and tumorigenicity was detected in vitro or in vivo after overexpression of miR-98. The target genes of miR-98 were predicted and verified by luciferase reporter assays. The effects miR-98/BCAT1 signaling on the chemoresistance and tumorigenicity of CD44+ GCSCs were investigated in a xenograft model by rescue experiments.Key FindingsWe have shown that miR-98 was decreased in CD44+ GCSCs. The overexpression of miR-98 could inhibit the expression of stem-related genes and the ability of self-renewal, invasion, and tumorigenicity of GCSCs. Also, we found that miR-98 overexpression enhances the sensitivity to cisplatin treatment in vitro. Using a xenograft model, we showed that miR-98 overexpression reversed paclitaxel resistance to CD44+ GCSCs. Finally, we found that branched-chain aminotransferases 1 (BCAT1) is a target gene of miR-98. Overexpressed BCAT1 reversed xenograft tumor formation ability and attenuated the paclitaxel chemosensitivity induced by miR-98 downregulation. Furthermore, BCAT1 restoration affected the expression of invasion and drug resistance-related genes.SignificanceThis study revealed miR-98 inhibits gastric cancer cell stemness and chemoresistance by targeting BCAT1, suggesting that this miR-98/BCAT1 axis represents a potential therapeutic target in gastric cancer.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

46 keywords...

hide…