Down-regulated lncRNA SBF2-AS1 in M2 macrophage-derived exosomes elevates miR-122-5p to restrict XIAP, thereby limiting pancreatic cancer development.
J Cell Mol Med
; 24(9): 5028-5038, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32301277
ABSTRACT
Evidence has indicated that M2 macrophages promote the progression of cancers, but few focus on the ability of M2 macrophage-derived exosomes in pancreatic cancer (PC). This study aims to explore how M2 macrophages affect malignant phenotypes of PC through regulating long non-coding RNA SET-binding factor 2 antisense RNA 1 (lncRNA SBF2-AS1)/microRNA-122-5p (miR-122-5p)/X-linked inhibitor of apoptosis protein (XIAP) axis. THP-1 cells were transformed into M1 macrophages by lipopolysaccharide and interferon-γ treatment, and into M2 macrophages after interleukin-4 treatment. The PANC-1 PC cell line with the largest lncRNA SBF2-AS1 expression was selected, and M2 macrophage-derived exosomes were isolated and identified. A number of assays were applied for the examination of lncRNA SBF2-AS1 expression, PC cell biological functions and subcellular localization of lncRNA SBF2-AS1. XIAP expression was detected, along with the interaction among lncRNA SBF2-AS1, miR-122-5p and XIAP. M2 macrophage exosomal lncRNA SBF2-AS1 expression's effects on the tumorigenic ability of PANC-1 cells in nude mice were also investigated. M2 macrophage-derived exosomes promoted progression of PC cells. Overexpressed lncRNA SBF2-AS1 promoted progression of PC cells. LncRNA SBF2-AS1 was found to act as a competing endogenous RNA to repress miR-122-5p and up-regulate XIAP. Constrained lncRNA SBF2-AS1 in M2 macrophage-derived exosomes contributed to restraining tumorigenic ability of PC cells. Collectively, our study reveals that constrained lncRNA SBF2-AS1 in M2 macrophage-derived exosomes increases miR-122-5p expression to restrain XIAP expression, which further inhibits PC progression.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Regulação Neoplásica da Expressão Gênica
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Oligonucleotídeos Antissenso
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MicroRNAs
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Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X
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Proteínas Tirosina Fosfatases não Receptoras
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RNA Longo não Codificante
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Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article