Background: Brain metastasis is a major cause for cancer death in patients with lung cancer. Sirtuin 1 (SIRT1) and hsa-miR-217 has been identified to mediate the development of non-small cell lung cancer (NSCLC). Aims: We performed this study to investigate the roles of hsa-miR-217, its target SIRT1, as well as P53/KAI1 axis in the brain metastasis from NSCLC. Study design: This is a cell culture study. Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or SIRT1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to SIRT1 was examined using dual luciferase reporter assay. Cell proliferation, migration, invasion and the expression of relate proteins were detected to examine the effect of miR-217/SIRT1 expression on metastasis. Results: PC-14/B cells expressed higher SIRT1 and lower p53 and KAI1 compared with BEAS-2B control cells (P<0.05). SIRT1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (P=0.004), migration (P=0.001) and proliferation (P<0.05), whereas SIRT1 overexpression reversed all processes. SIRT1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase (MMP)-9 and beta-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes. Conclusions: Hsa-miR-217 and its target SIRT1 acted as metastasis suppressor and promoter gene in NSCLC, respectively. The hsa-miR-217/SIRT1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from NSCLC. This axis might be a potential target for the treatment of brain metastasis of lung cancer.
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