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miR-200c/PAI-2 promotes the progression of triple negative breast cancer via M1/M2 polarization induction of macrophage.
- Source :
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International Immunopharmacology . Apr2020, Vol. 81, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
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Abstract
- • miR-200c overexpression upregulated PAI-2 in TNBC. • miR-200c/PAI-2 increased macrophages. • miR-200c/PAI-2 promotes the progression of TNBC by inducing macrophage polarization. To investigate the effect of miR-200c/PAI-2 on macrophage polarization into M2-type TAMs in TNBC. PAI-2 expression in MDA-MB-231con, MDA-MB-231miR-200ab and MDA-MB-231miR-200c breast cancer cells was evaluated by RT-PCR and immunofluorescence (IF), while the expression of the TAM marker F4/80 and the M2-type TAM marker CD206 in MDA-MB-231con, MDA-MB-231miR-200c and MDA-MB-231miR-200c/siPAI-2 mouse lung metastatic tumor tissues was examined with immunohistochemistry (IHC). The effects of RAW264.7 cells on MDA-MB-231con, MDA-MB-231miR-200c and MDA-MB-231miR-200c/siPAI-2 were examined by transwell co-culture. CD206 expression in RAW264.7 cells were confirmed by immunostaining. The level of PAI-2 and IL-10 in the co-culture supernatants were assessed using ELISA. 1. RT-PCR and IF analysis showed that PAI-2 was upregulated in MDA-MB-231miR-200c cells. 2. IHC assays analysis showed that the numbers of F4/80 and CD206 positive cells were increased in MDA-MB-231miR-200c tumor tissues, while in MDA-MB-231miR-200c/siPAI-2 tumor tissues were decreased. 3. Transwell co-culture assays analysis showed that MDA-MB-231miR-200c cells significantly promoted the cell migration ability compared with the control group, while knockdown PAI-2 significantly inhibited the cell migration ability (P < 0.05). 4. Transwell co-culture and immunostaining assays analysis showed that overexpression miR-200c in MDA-MB-231 cell line increased the CD206 expression in RAW264.7 cells, while knockdown PAI-2 decreased. 5. ELISA assays analysis showed that miR-200c-mediated MDA-MB-231 cells significantly increased the secretion of PAI-2 and IL-10, while decreased the secretion of PAI-2 and IL-10 in MDA-MB-231 miR-200c/siPAI-2 cells. miR-200c promotes the malignant progressions of TNBC by PAI-2 upregulation and M2 phenotype macrophages polarization. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MACROPHAGES
*TRIPLE-negative breast cancer
*CELL migration
Subjects
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 81
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 142365325
- Full Text :
- https://doi.org/10.1016/j.intimp.2019.106028