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Background and Purpose: Brain metastasis is among the leading causes of death in patients with non-small-cell lung cancer (NSCLC). Through yet unknown mechanisms, prophylactic cranial irradiation (PCI) can significantly decrease the incidence of brain metastases. Given that PCI probably exerts indirect anti-tumoral effects by turning cerebral "soil" unfavorable for the colonization of metastatic tumor "seeds". This study aims to reveal how PCI regulates the brain microenvironment conducing to a reduction in brain metastases. Materials and Methods: Key markers of M1/M2 microglia types and mesenchymal-to-epithelial transition (MET) were analyzed by qRT-PCR and Western Blot in vitro. The target miR-9 was obtained by miRNA array analysis and confirmed by qRT-PCR in microglia. We used miRTarBase and TargetScan to analyze the target genes of miR-9 and confirmed by luciferase activity assay. Anti-metastatic effects of irradiation on the brain were evaluated by intravital imaging using a brain metastatic A549-F3 cell line in a nude mouse model. Results: Irradiation induced M1 microglia activation, which inhibited the MET process of A549 cell lines. Furthermore, levels of miR-9 secreted by irradiated M1 microglia significantly increased and played a vital role in the inhibition of the A549 MET process by directly targeting CDH1, concurrently decreasing cell capacity for localization in the brain, thus reducing brain metastases. Conclusion: We demonstrated that miR-9 secreted by irradiated M1-type microglia played an important role in modulating A549 cell lines into mesenchymal phenotype and further decreased their localization capabilities in the brain. Our findings signify the modulating effect of irradiation on metastatic soil and the cross-talk between tumour cells and the metastatic microenvironment; importantly, they provide new opportunities for effective anti-metastasis therapies, especially for brain metastasis patients. [ABSTRACT FROM AUTHOR]

Brain metastasis, one of the common complications of lung cancer, is an important cause of death in patients with advanced cancer, despite progress in treatment strategies. Lung cancers with positive driver genes have higher incidence and risk of brain metastases, suggesting that driver events associated with these genes might be biomarkers to detect and prevent disease progression. Common lung cancer driver genes mainly encode receptor tyrosine kinases (RTKs), which are important internal signal molecules that interact with external signals. RTKs and their downstream signal pathways are crucial for tumor cell survival, invasion, and colonization in the brain. In addition, new tumor driver genes, which also encode important molecules closely related to the RTK signaling pathway, have been found to be closely related to the brain metastases of lung cancer. In this article, we reviewed the relationship between lung cancer driver genes and brain metastasis, and summarized the mechanism of driver gene-associated pathways in brain metastasis. By understanding the molecular characteristics during brain metastasis, we can better stratify lung cancer patients and alert those at high risk of brain metastasis, which helps to promote individual therapy for lung cancer. [ABSTRACT FROM AUTHOR]