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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Exosomal microRNA-588 from M2 polarized macrophages contributes to cisplatin resistance of gastric cancer cells
Hai-Yan Cui, Jian-Sheng Rong, Ju Chen, Jie Guo, Jia-Qin Zhu, Mei Ruan, Rong-Rong Zuo, Shuang-Shuang Zhang, Jun-Mei Qi, Bao-Hua Zhang
Hai-Yan Cui, Rong-Rong Zuo, Shuang-Shuang Zhang, Jun-Mei Qi, Department of Pathology, The Fourth People’s Hospital of Zibo City, Zibo 255000, Shandong Province, China
Jian-Sheng Rong, Bao-Hua Zhang, Department of Pathology, Zibo Central Hospital, Zibo 255036, Shandong Province, China
Ju Chen, Department of Ultrasound Medicine, Zibo Central Hospital, Zibo 255036, Shandong Province, China
Jie Guo, Department of Health, The Fourth People’s Hospital of Zibo City, Zibo 255000, Shandong Province, China
Jia-Qin Zhu, Department of Gastroenterology, The Fourth People’s Hospital of Zibo City, Zibo 255000, Shandong Province, China
Mei Ruan, Department of Oncology, The Fourth People’s Hospital of Zibo City, Zibo 255000, Shandong Province, China
Author contributions: Cui HY, Rong JS, and Chen J designed the study; Guo J, Zhu JQ, and Ruan M performed the experiments; Zuo RR and Zhang SS collected and analysed the data; Qi JM and Zhang BH wrote the manuscript.
Institutional review board statement: This study was reviewed and approved by the Zibo Central Hospital.
Institutional animal care and use committee statement: All animal experiments in this study were approved by the Zibo Central Hospital.
Conflict-of-interest statement: The authors declare no conflict of interest for this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Bao-Hua Zhang, MSc, Chief Physician, Department of Pathology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zhangdian District, Zibo 255036, Shandong Province, China. zhangbaohua314@163.com
Received: April 23, 2021
Peer-review started: April 23, 2021
First decision: May 27, 2021
Revised: June 7, 2021
Accepted: August 11, 2021
Article in press: August 11, 2021
Published online: September 28, 2021
BACKGROUND
Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally. Cisplatin (DDP) is one of the most common and effective chemotherapies for patients with gastric cancer, but DDP resistance remains a severe clinical challenge.
AIM
To explore the function of M2 polarized macrophages-derived exosomal microRNA (miR)-588 in the modulation of DDP resistance of gastric cancer cells.
METHODS
M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis. The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers. The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells. The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay, apoptosis analysis, colony formation assay, Western blot analysis, qPCR analysis, and luciferase reporter assay in SGC7901 and SGC7901/DDP cells, and by tumorigenicity analysis in nude mice.
RESULTS
M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin (IL)-13 and IL-4. Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance. M2 polarized macrophages-derived exosomes could transfer in gastric cancer cells to enhance DDP resistance. Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells. miR-588 promoted DDP-resistant gastric cancer cell growth in vivo. miR-588 was able to target cylindromatosis (CYLD) in gastric cancer cells. The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP.
CONCLUSION
In conclusion, we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD. miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.
Core Tip: In this study, we uncovered that exosomal miR-588 from M2 macrophages contributes to cisplatin resistance of gastric cancer cells by partly targeting cylindromatosis. miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.
