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 500 μM) group was detected compared with that in the control group in 95D cells in vitro. Subsequently, we demonstrated that 50 μM 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.

中文翻译：

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miR-30b参与犬尿氨酸介导的赖氨酰氧化酶表达。

微环境成分通过调节控制转移的关键分子来深刻影响癌症转移的倾向。赖氨酰氧化酶（LOX）有助于细胞外基质（ECM）的重塑，并最终促进乳腺癌的骨转移。微环境成分Kynurenine（Kyn）能够调节癌细胞的生物学行为，例如在体内促进结节转移。但是，尚不清楚Kyn是否控制LOX的生成。在本研究中，在体外95D细胞中，与对照组相比，Kyn（30、50、100、200和500μM）组的迁移明显增加。随后，我们证明了50μMKyn不仅显着上调了LOX的mRNA和分泌水平，而不仅是细胞质LOX，但同时也显着降低了miR-30b的水平。此外，双荧光素酶测定系统也证实了LOX mRNA和miR-30b之间的直接相互作用。最重要的是，不仅在miR-30b模拟治疗中Kyn诱导的LOX mRNA的增加显着减弱，而且在Kyn介导的mRNA上调中，Kyn介导的LOX分泌水平在miR-30b抑制剂治疗中明显增强。这些结果表明，miR-30b参与Kyn介导的LOX表达。miR-30b抑制剂治疗可显着增强LOX的分泌水平。这些结果表明，miR-30b参与Kyn介导的LOX表达。miR-30b抑制剂治疗可显着增强LOX的分泌水平。这些结果表明，miR-30b参与Kyn介导的LOX表达。