Research Paper Volume 12, Issue 19 pp 19660—19676
Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells
- 1 Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
- 2 Department of Ultrasonography, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
Received: May 13, 2020 Accepted: August 5, 2020 Published: October 11, 2020
https://doi.org/10.18632/aging.103997How to Cite
Copyright: © 2020 Xu 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.
Abstract
Objective: This study aims to explore the roles of miR-124 in pancreatic tumor and potential vehicles.
Results: The miR-124 expression levels decreased in pancreatic adenocarcinoma tissues and cancer cell lines AsPC-1, PANC1, BxPC-3 and SW1990. Furthermore, the elevated expression of miR-124 in AsPC-1 and PANC1 via miR-124 mimic transfection-induced apoptosis, metastasis and epithelial mesenchymal transition was suppressed, and the EZH2 overexpression partly reversed the protective effects of miR-124 against pancreatic tumors. In addition, the expression of miR-124 was detected in exosomes extracted from miR-124-transfected BM-MSCs, and these exosomes delivered miR-124 into pancreatic cancer cells, and presented the anti-tumor effects in vitro and in vivo.
Conclusion: MiR-124-carried BM-MSC-derived exosomes have potential applications for the treatment of pancreatic tumors.
Methods: The expression of miR-124 and EZH2 was determined in both pancreatic cancer tissues and cell lines. miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability. apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. Afterwards, the roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice.
Abbreviations
BM-MSCs: Bone marrow mesenchymal stromal cells; PDAC: Pancreatic ductal adenocarcinoma; 5-FU: Fluorouracil; miRNAs: MicroRNAs; H&E: Hematoxylin and eosin; DMSO: Dimethyl sulphoxide; RT: Reverse-transcribed; FBS: Fetal bovine serum; EMT: Epithelial mesenchymal transition P3; P3: Passage 3.