MicroRNA Signatures in Lung Adenocarcinoma Metastases: Exploring the Oncogenic Targets of Tumor-Suppressive and .

: To improve the prognosis of patients with lung adenocarcinoma (LUAD), revolutionary treatments for metastatic lesions are essential. : To identify genes closely involved in LUAD-cell-derived metastasis, we used RNA sequencing to generate microRNA (miRNA) expression signatures of brain metastatic lesions. Once tumor-suppressive miRNAs are identified, it will be possible to explore the numerous tumor-promoting genes that are regulated by miRNAs. : By comparison with a previously created LUAD signature, we identified several miRNAs whose expression was significantly suppressed in brain metastases. We focused on both strands of pre- ( and ), which were significantly downregulated in brain metastatic tissues, and confirmed by ectopic expression assays that both strands of pre- attenuated the aggressive phenotypes (cell proliferation, migration, and invasion) of LUAD cells. These data suggest that both strands of pre- have tumor-suppressive functions in LUAD cells. Next, we explored the target molecules that each miRNA strand regulates in LUAD cells. We identified 159 target genes regulated by and , of which 12 genes (, , , , , , , , , , , and ) affect cell cycle/cell division and the prognosis of LUAD patients. Finally, we focused on two genes, ( target) and ( target), and demonstrated their oncogenic functions and the molecular pathways they regulate in LUAD cells. : The miRNA signature derived from lung cancer brain metastasis will be a landmark in the field, and analysis of this miRNA signature will accelerate the identification of genes involved in lung cancer brain metastasis.