Effects Of MiR382-overexpressing Tumorassociated Macrophages On The Biological Characteristics Of Triple-negative Breast Cancer And Possible Mechanisms

Objective: To investigate the effect of micro RNA-382(miR-382)in tumor-associated macrophages(TAMs)on the biological characteristics of triple negative breast cancer cells in vitro.Methods: Real-time PCR(qRT-PCR)and immunocytochemistry were performed to examine the effects of lentivirus-mediated mi R-382 overexpression in mouse peritoneal macrophages(PMs).Western blotting was used to detect the changes of protein expression of the polarization index of TAMs(IL-10 and TNF-?),PGC-1 alpha and NF-kappa B,qRT-PCR was used to detect the changes of nucleic acid of miR-382,the polarization index of TAMs(IL-10 and TNF-?)and PGC-1 alpha,in triple negative breast cancer conditioned medium(TCM)stimulated PMs with or without miR-382 over-expression.Flow cytometry was used to detect the polarization of TAMs(CD86 and CD206)and the apoptosis rate of 4T1 cells and the cell cycle.Transwell invasion assay was used to detect the invasion ability of 4T1 cells.The expression of PGC-1 alpha and NF-kappa B was detected by laser confocal microscope imaging.Results: Through the TCM stimulation of PMs,TAMs showed M2-type polarization,miR-382 expression decreased,PGC-1? expression increased and NF-kappa B transcriptional activity decreased,and the invasion ability of 4T1 cells increased,apoptosis rate decreased.After lentiviral transfection,the PMs were overexpressed by mi R-382 and then stimulated by TCM.It was found that TAMs were polarized towards M1,the expression of miR-382 was increased,the expression of PGC-1? was decreased,NF-kappa B transcriptional activity increased and the invasion ability of 4T1 cells was decreased,the apoptosis rate was increased.Conclusion TAMs can inhibit the invasion and proliferation of triplenegative breast cancer by regulating the expression of miR-382,which may be related to the inhibition of the expression of PGC-1? by miR-382,the transcriptional activity of NF-kappa B and the inhibition of M2 differentiation of TAMs.