Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

Xiang Ying; Quanfeng Wu; Xiaoli Wu; Qinyi Zhu; Xinjing Wang; Lu Jiang; Xin Chen; Xipeng Wang

doi:10.18632/oncotarget.9246

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Research Papers:

Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

Xiang Ying, Quanfeng Wu, Xiaoli Wu, Qinyi Zhu, Xinjing Wang, Lu Jiang, Xin Chen and Xipeng Wang _

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Oncotarget. 2016; 7:43076-43087. https://doi.org/10.18632/oncotarget.9246

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Abstract

Xiang Ying1,*, Quanfeng Wu1,*, Xiaoli Wu1, Qinyi Zhu1, Xinjing Wang1, Lu Jiang1, Xin Chen1, Xipeng Wang1

1Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

*These authors are contributed equally to this work

Correspondence to:

Xipeng Wang, email: [email protected]

Keywords: exosomes, miR-222-3p, macrophage, polarization, epithelial ovarian cancer

Received: February 18, 2016 Accepted: April 19, 2016 Published: May 09, 2016

ABSTRACT

Cancer secreted exosomal miRNAs are emerging as mediators between tumor-stoma crosstalk. Here, we show epithelial ovarian cancer (EOC)-derived exosomes activated macrophages to a tumor-associated macrophage (TAM)-like phenotype with SOCS3/STAT3 pathway involvement, which could facilitate the progression of cancer. MiR-222-3p was enrichment in exosomes released from EOC cells and it could be transferred to macrophages. Overexpression of miR-222-3p in macrophages induced polarization of the M2 phenotype. Luciferase assay verified miR-222-3p targeted SOCS3 genes and expression of SOCS3 was decreased after transfection with a miR-222-3p mimic. Down-regulation of SOCS3 correlated with an increased expression of STAT3 activation. MiR-222-3p could be detected in the exosomes from serum and its levels were related to EOC. These observations propose tumor-derived exosomal miR-222-3p is an effective regulator in the polarization of tumor-promoting M2 macrophages and may be a biomarker of EOC.

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Research Papers:

Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

Abstract