Abstract: Objective To investigate the role and regulatory mechanism of miR-139-5p in the progression of lung adenocarcinoma (LUAD). Methods The expression levels of miR-139-5p andNotch homolog 1 (Notch1) in LUAD tissues and cells were detected and the transfection efficiency after cell transfection was verified by Quantitative real-time PCR ( qRT-PCR) and Western blotting. The proliferation, migration and invasion of LUAD cells were determined by CCK-8, wound healing and Transwell assay. The targeting relationship of miR-139-5p to Notch1 was analyzed using a dual luciferase reporter gene assay. Western blotting was employed to detect the expression levels ofPI3K / AKT / mTOR signaling pathway related proteins. Results miR-139-5p was significantly downregulated (P < 0. 01) and Notch1 was significantly up-regulated in the LUAD tissues and cells (P < 0. 01), when compared with those in the normal tissues and human normal bronchial epithelialcells. miR-139-5p overexpression suppressed the proliferation, migration and invasion of LUADcells, and down-regulated the expression levels of p-PI3K, p-AKT and p-mTOR ( P < 0. 01 ).Notch1 was identified as a target of miR-139-5p that could directly bind to it. Overexpression of Notch1 attenuated the inhibitory effects of miR-139-5p on proliferation, migration and invasion ofLUAD cells (P < 0. 05). In vivo experiment showed that the overexpression of miR-139-5p inhibited the growth of xenograft tumor in nude mice when compared with that in the control group ( P < 0. 05). Conclusion miR-139-5p inhibits the proliferation, migration and invasion of LUAD cellsby targeting Notch1 and inactivation of PI3K / Akt / mTOR pathway.

Key words: lung adenocarcinoma, miR-139-5p, Notch1, migration, invasion