Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk.
Animals
Carcinogenesis
/ immunology
Cell Line, Tumor
Circulating MicroRNA
/ blood
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ immunology
Humans
Lung
/ pathology
Lung Neoplasms
/ blood
Macrophages
/ immunology
Male
Mice
Mice, SCID
MicroRNAs
/ blood
Neutrophils
/ immunology
STAT4 Transcription Factor
/ genetics
Tobacco Smoking
/ blood
Tumor Escape
/ genetics
Xenograft Model Antitumor Assays
lung cancer
microRNA
microenvironment
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 06 2019
01 06 2019
Historique:
received:
13
09
2018
revised:
29
10
2018
accepted:
06
11
2018
pubmed:
15
11
2018
medline:
4
9
2019
entrez:
15
11
2018
Statut:
ppublish
Résumé
miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell-type specific expression pattern and topography of several miRNAs such as mir-145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells was observed in normal and lung cancer tissues. Granulocytes and platelets are the major contributors of miRNAs release in blood. miRNAs modulation observed in plasma of lung cancer subjects was consistent with de-regulation of the same miRNAs observed during immunosuppressive conversion of immune cells. In particular, activated neutrophils showed a miRNA profile mirroring that observed in plasma of lung cancer subjects. Interestingly mir-320a secreted by neutrophils of high-risk heavy-smokers promoted an M2-like protumorigenic phenotype through downregulation of STAT4 when shuttled into macrophages. These findings suggest a multifactorial and nonepithelial cell-autonomous origin of circulating miRNAs associated with risk of lung cancer and that circulating miRNAs may act in paracrine signaling with causative role in lung carcinogenesis and immunosuppression.
Identifiants
pubmed: 30426475
doi: 10.1002/ijc.31988
pmc: PMC6590261
doi:
Substances chimiques
Circulating MicroRNA
0
MIRN320 microRNA, human
0
MicroRNAs
0
STAT4 Transcription Factor
0
STAT4 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2746-2761Subventions
Organisme : NCI NIH HHS
ID : U01 CA166905
Pays : United States
Informations de copyright
© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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