Involvement of miR-30b in kynurenine-mediated lysyl oxidase expression.

Abstract

Microenvironment components profoundly influence the propensity of cancer metastasis through regulating key molecules controlling metastasis. Lysyl oxidase (LOX) contributes to extracellular matrix (ECM) remodeling, and finally promoting bone metastasis in breast cancer. Kynurenine (Kyn), a microenvironment component, is capable of regulating the biological behaviors of cancer cells, such as promoting node metastasis in vivo. However, it is still unclear whether Kyn controls the generation of LOX. In the current study, a significant increase of migration in the Kyn (30, 50, 100, 200, and 500μM) group was detected compared with that in the control group in 95D cells in vitro. Subsequently, we demonstrated that 50μM Kyn not only substantially upregulated the mRNA and secreted levels of LOX rather than cytoplasmic LOX, but also markedly reduced the level of miR-30b at the same time. Furthermore, the direct interaction between LOX mRNA and miR-30b was also confirmed by dual-luciferase assay system. Most importantly, not only was Kyn-induced increase of LOX mRNA significantly attenuated on miR-30b mimics treatment, but also Kyn-mediated the upregulation of the mRNA, and secreted levels of LOX were distinctly strengthened on miR-30b inhibitor treatment. These results suggest that miR-30b is involved in Kyn-mediated LOX expression.