Haifeng Qin,1 Jiping Sha,2 Caixia Jiang,3 Xuemei Gao,2 Lili Qu,1 Haiying Yan,4 Tianjiao Xu,5 Qiyu Jiang,6 Hongjun Gao1 1Department of Pulmonary Neoplasm Internal Medicine, Affiliated Hospital of Academy of the Military Medical Sciences, Beijing, 2Department of Rehabilitation, Zhangqiu City People’s Hospital, Zhangqiu, 3Department of Endocrinology, Zhangqiu City People’s Hospital, Zhangqiu, 4Department of Oncology, Cancer Hospital of Ci County, Handan, 5Department of Oncology, 477 Hospital of People’s Liberation Army, Xiangyang, 6Center of Technical and Service, the 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China Abstract: miR-122 may function as a novel tumor suppressor. Expression of miR-122 could suppress the proliferation of multi-kinds of human cancer cell lines. In this work, expression of miR-122 via adenoviral vector in non-small-cell lung cancer (NSCLC) cells reduces the number of invasion and migration cells. miR-122 attenuates the epithelial–mesenchymal transition process, which mediates cancer cells metastasis in NSCLC cells A549 and H460. The mechanisms data reveals that miR-122 would disrupt the epithelial–mesenchymal transition process by downregulating PI3K/AKT activation via reducing endogenous expression of insulin-like growth factor 1 receptor. These data highlight the detailed roles and potential application of miR-122 in NSCLC cells. Keywords: microRNA-122, tumor suppressor, metastasis, epithelial–mesenchymal transition, PI3K/AKT signaling pathway