Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells.

Yan Xu,Baomin Shi,Deren Zhou,Xiuyan Wang,Yuhua Wei,Nanbin Liu,Rui Lin

doi:10.18632/aging.103997

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.

Highlights

Pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), is one of main threats for public health, pancreatic cancer is not the most common cancer type
MiR-124 expression was downregulated and the expression of EZH2 was stimulated in pancreatic cancer tissues and cell lines, First, reverse transcriptionpolymerase chain reaction (RT-PCR) was performed to examine the miR-124 and EZH2expression in pancreatic cancer tumor tissues
The results revealed that the miR-124 expression significantly decreased in pancreatic tumors, while the EZH2 expression in pancreatic cancer tissues was remarkably elevated (Fig. 1A)

Summary

Introduction

Pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), is one of main threats for public health, pancreatic cancer is not the most common cancer type. The mortality of pancreatic cancer accounted for 4.5% of all cancers, which is almost double of its incidence [2]. One fifth of pancreatic cancers cases occur in China, among which nearly 40% were under 65 years old [3]. The best strategy for pancreatic cancer therapy is surgical resection, as long as it can be detected early, because surgery provides good short-term outcomes. There is a real challenge for pancreatic cancer diagnosis, because this presents with very few typical symptoms [1, 4]. Merely few pancreatic cancer patients are suitable for surgery. The reason for this is that many patients presented with transforming diseases when upon diagnosis, which lead to poor prognosis[1, 5]. There is need to identify new weapons against pancreatic cancer

Methods

Results

Discussion

Conclusion