Dataset Information

The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.

ABSTRACT: Pancreatic cancer (PC) remains a major health concern, with conventional cancer treatments exerting little influence on the disease course. MicroRNA-520b (miR-520b) functions as a tumor suppressor in several types of human cancers, whereas its anti-tumor property in the context of PC is still fundamental. The aim of this study is to identify the potential therapeutic role of miR-520b, transferred by exosomes, derived from normal fibroblasts (NFs) in PC progression. A gain-of-function study was performed to examine the roles of miR-520b in PC cell line SW1990, which suggested that miR-520b served as a tumor suppressor in PC. In order to confirm the role of exosomal miR-520b, exosomes were isolated from NF culture medium and cocultured with SW1990 cells. During the coculture experiments, we disrupted exosome secretion and upregulated exosomal miR-520b. The in vitro coculture studies revealed that miR-520b was transferred from NF-derived exosomes to PC cells and thereby suppressed PC cell proliferation, invasion, migration, and stimulated apoptosis. Furthermore, inhibited tumor growth and live metastasis upon elevated miR-520b in exosomes were observed in vivo. Conjointly, our study demonstrates that NF-derived exosomal miR-520b impedes the progression of PC, which contributes to a novel, therapeutic role of exosomal miR-520b for treating PC.

SUBMITTER: Shi H

PROVIDER: S-EPMC7090279 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.

Shi Huijuan H Li Hui H Zhen Tiantian T Dong Yu Y Pei Xiaojuan X Zhang Xiangliang X

Molecular therapy. Nucleic acids 20200110

Pancreatic cancer (PC) remains a major health concern, with conventional cancer treatments exerting little influence on the disease course. MicroRNA-520b (miR-520b) functions as a tumor suppressor in several types of human cancers, whereas its anti-tumor property in the context of PC is still fundamental. The aim of this study is to identify the potential therapeutic role of miR-520b, transferred by exosomes, derived from normal fibroblasts (NFs) in PC progression. A gain-of-function study was p ...[more]

PMID: 32200272

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Project description:Myocardial infarction arises from an excessive or prolonged inflammatory response, leading to ventricular remodeling or impaired cardiac function. Macrophages exhibit different polarization types associated with inflammation both at steady state and after myocardial infarction. Exosomal miR-146a-5p has been identified as an important molecule in the cardiovascular field in recent years. However, the effect of cardiomyocyte-derived exosomal miR-146a-5p on macrophages has not yet been elucidated. Initially, we found that exosomes with low expression of miR-146a-5p derived from myocardial infarction tissues modulated macrophage polarization. To determine whether cardiomyocyte-derived exosomal miR-146a-5p mediated macrophage polarization, we treated macrophages with exosomes rich in miR-146a-5p collected from neonatal mouse cardiomyocytes. The effects of exosomal miR-146a-5p on macrophage polarization were measured using RT-qPCR, transwell assays, and western blotting. The results showed that the increased expression of miR-146a-5p promoted M1 macrophage polarization, inhibited M2 macrophage polarization, and increased the expression of VEGFA. However, the decreased expression of exosomalmiR-146a-5p showed the opposite trends. Interestingly, in contrast to treatment with the solitary miR-146a-5p mimic, exosomal miR-146a-5p derived from neonatal mouse cardiomyocytes reduced TNFα and iNOS expression. In addition, when macrophages were activated by the miR-146a-5p mimic or exosomal miR-146a-5p, the expression of TNF receptor-associated factor 6 (TRAF6), a target gene of miR-146a-5p, was reduced significantly. Taken together, these findings indicate that exosomal miR-146a-5p derived from cardiomyocytes could stimulate M1 macrophage polarization to induce an inflammatory reaction, while targeting TRAF6, exerting an anti-inflammatory effect. Exosomal miR-146a-5p plays important roles in macrophages, illuminating a novel potential therapeutic target in myocardial infarction.

Dataset Information

The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.

Publications

The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.

Similar Datasets

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