Knockdown of B7H6 inhibits tumor progression in triple-negative breast cancer.

The B7 family, the most common family of secondary signaling molecules, consists of eight cell-surface proteins, which regulate the T-cell mediated immune response by delivering co-inhibitory or co-stimulatory signals through their corresponding ligands. Among them, natural killer cell cytotoxicity receptor 3 ligand 1 (NCR3LG1, also known as B7H6) has been reported as a new member, and is involved in tumor progression of various types of human cancer. However, the role of B7H6 in triple-negative breast cancer (TNBC) remains unknown. In the present study, western blotting was performed to determine the protein expression levels of B7H6 in a normal mammary epithelial cell line (MCF-10A), non-TNBC breast cancer cell lines (MCF-7 and AU565) and TNBC cell lines (MDA-MB-231 and MDA-MB-468). B7H6 was knocked down using small interfering RNA, and an MTT assay was performed to determine proliferation ability, flow cytometry was used to analyze apoptosis, and Transwell and wound-healing assays were performed to measure migration ability. Expression of proliferation-associated proteins (SMAD family member 4 and β-catenin) and apoptosis-associated proteins (BCL2 associated X, BCL2 apoptosis regulator and caspase-3) were analyzed by western blotting. The results demonstrated that B7H6 was highly expressed in TNBC cells, and that knockdown of B7H6 inhibited cell proliferation and migration, and promoted apoptosis. Furthermore, the results revealed that proliferation and apoptosis-associated proteins were altered in the B7H6-knockdown MDA-MB-231 cells. In conclusion, the present study demonstrated that B7H6 may have significant roles in the regulation of cell proliferation, apoptosis and migration of TNBC cells.