The microRNA-152/human leukocyte antigen-G axis affects proliferation and immune escape of non-small cell lung cancer cells

Abstract

Objective: To investigate the role of human leukocyte antigen (HLA-G) on proliferation, invasion, and immune escape in non-small cell lung cancer (NSCLC). Methods: The relationship between HLA-G and overall survival (OS) of NSCLC patients was analyzed using the KMPlot database. The expression of micro (mi)R-152 or HLA-G was modulated by transfecting synthetic oligonucleotides, and the impact of the miR-152/HLA-G axis on proliferation, invasion, colony formation in soft agar, and tolerance to natural killer (NK) cell cytolysis was measured. Results: Bioinformatics analysis showed that high HLA-G expression was correlated with poor OS in NSCLC patients. The tolerance of NSCLC cells to NK cytotoxicity was negatively correlated with HLA-G and positively correlated with miR-152 expression. Over-expressing miR-152 inhibited HLA-G expression in A549 cells and attenuated cell proliferation, migration, colony formation ability, and tolerance to NK cells. However, blocking HLA-G expression by small interfering RNA did not affect migration or colony formation, but only proliferation and tolerance to NK cells in vitro and in vivo. Blocking Ig-like transcript 2 on the surface of NK cells increased their killing effect in the presence of high HLA-G expression. Conclusions: miR-152/HLA-G axis plays an oncogenic role in NSCLC by affecting cell proliferation and immune escape.