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MiR-217 Inhibits M2-Like Macrophage Polarization by Suppressing Secretion of Interleukin-6 in Ovarian Cancer

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Abstract

Ovarian cancer is one of the most deadly cancers with rapid proliferation and poor prognosis among patients. Therapies focusing on regulation of tumor immunity and microenvironments are developing. MiR-217 was dysregulated in cancer progress and plays important roles in tumorigenesis and metastasis. However, the role of miR-217 in regulation of macrophage polarization and its underlying molecular mechanism remain unclear. The expression of miR-217 in ovarian cancerous tissues and cell lines were assessed by qRT-PCR. And we detected the staining of CD86 and CD206 via flow-cytometry and the levels of Arg-1 and CCR2 by western-blot in order to evaluate M2 macrophage polarization. The targeting regulation of miR-217 on pro-inflammatory factor IL-6 was assessed by dual-luciferase reporter assay and western-blot. ELISA assay was used to evaluate the secretion of IL-6 and IL-10 of cells. MiR-217 was found to be downregulated in ovarian cancerous tissues and cell lines. This downregulation correlated with an increased expression of the IL-6, Arg-1, CCR2, and CD206 gene. The overexpression of miR-217 in SKOV3 cells can inhibit the polarization of macrophages towards an M2-like phenotype. We also found that IL-6 was validated to induce M2 macrophage polarization and its secretion in SKOV-3 cells was inhibited by miR-217 directly. Moreover, we revealed that miR-217 suppressed M2 macrophage polarization partly thought JAK/STAT3 signal pathway. Taken together, these findings indicate that miR-217 inhibits tumor-induced M2 macrophage polarization through targeting of IL-6 and regulation JAK3/STAT3 signaling pathway, which may provide a potential therapeutic target for treating ovarian cancer.

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Acknowledgments

We would like to give our sincere gratitude to the reviewers for their constructive comments.

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  1. Department of Gynaecology, The Third Xiangya Hospital of Central South University, No. 178, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People’s Republic of China

    Bin Jiang, Shu-Juan Zhu, Song-Shu Xiao & Min Xue

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Jiang, B., Zhu, SJ., Xiao, SS. et al. MiR-217 Inhibits M2-Like Macrophage Polarization by Suppressing Secretion of Interleukin-6 in Ovarian Cancer. Inflammation 42, 1517–1529 (2019). https://doi.org/10.1007/s10753-019-01004-2

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