The Effect of on Macrophage Polarization and T Cell Immunity by Targeting in Breast Cancer.

BACKGROUND

Breast cancer is the most common cancer in women. had binding sites with through the bioinformatics prediction. But few studies have been conducted on and in breast cancer. We aimed to explore the effect of and on breast cancer and the mechanisms involved.

METHODS

Clinical samples of breast cancer were collected. Bioinformatics analysis was performed to screen the differentially expressed miRNAs. CD4 T cells and CD8 T cells were cocultured with MCF-7 cells in the Transwell system. Moreover, MCF-7 cells and M0 macrophage cocultured cell lines were constructed. qRT-PCR, IF, western blot, flow cytometry, and ELISA were performed to detect related factors expression. Starbase and dual-luciferase reporter assay verified the binding of to . The tumor formation model was established to study and effects .

RESULTS

The differentially expressed was screened via miRNAs sequencing and cell verification. expression was high, was low in tumor tissues, T cells and NK cells were inhibited, and macrophages were transformed into M2 type, promoting immune escape. In addition, bound to . Then, splenic CD4 T cells and CD8 T cells were successfully sorted. During CD4 T cell differentiation to Th1 and Treg, Th1 was inhibited, and Treg was activated. We found the polarization of macrophages was related to breast cancer. The proportion of CD206 cells increased and CD68 cells decreased in the mimics group compared with the mimic NC group. Compared with the inhibitor NC group, the proportion of CD206 cells decreased, and CD68 cells increased in the inhibitor group. experiments showed that inhibitor inhibited tumor growth and promoted expression. The proportion of CD3, CD4, CD8, NK1.1, CD4+IFN, and CD68 cells increased, while FOXP3 and CD206 cells decreased in the inhibitor group compared with the inhibitor NC group. However, the proportion of CD3, CD4, CD8, NK1.1, CD4+IFN, and CD68 cells decreased, while FOXP3 and CD206 cells increased after the addition of si.

CONCLUSIONS

inhibited and aggravated breast tumors. inhibitor enhanced CD4 and CD8 cell populations in the tumor immune microenvironment and inhibited tumor growth.