miR-98-5p inhibits gastric cancer cell stemness and chemoresistance by targeting branched-chain aminotransferases 1.

Abstract

AIMS:

Gastric 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 METHODS:

The 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 FINDINGS:

We 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.

SIGNIFICANCE:

This 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.

• Authors: Panpan Zhan, Xiong Shu, Meng Chen, Lixin Sun, Long Yu, Jun Liu, Lichao Sun, Zhihua Yang, Yuliang Ran
• Journal: Life sciences (Life Sci) Vol. 276 Pg. 119405 (Jul 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33798550 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• CD44 protein, human
• Hyaluronan Receptors
• MIRN98 microRNA, human
• MicroRNAs
• BCAT1 protein, human
• Transaminases
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic
• Humans
• Hyaluronan Receptors (metabolism)
• Male
• Mice
• Mice, Nude
• MicroRNAs (genetics)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Prognosis
• Stomach Neoplasms (drug therapy, genetics, metabolism, pathology)
• Transaminases (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays