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Previous studies have shown that the expression of microRNA-4458 (miR-4458) is dysregulated in hepatocellular carcinoma and colon cancer.In this study,we investigated the direct target of miR-4458 and its biological functions in human lung cancer cells.By using the database TargetScan,we identified Lin28B,an oncogene,as a direct target gene of miR-4458.In dual-luciferase reporter assay,we found that miR-4458 mimics dose-dependently inhibited the luciferase activity of the wild-type 3’UTR of Lin28B in human lung cancer A549 and NCl-H1299 cell lines without affecting its mutant forms,whereas anti-miR-4458,an inhibitor of miR-4458,dose-dependently promoted the luciferase activity of the wild-type 3’UTR of Lin28B in A549 and NCl-H1299 cell lines without affecting its mutant forms.Overexpression of miR-4458 significantly decreased the protein levels of Lin28B in the cells,and inhibited the cell growth and colony formation.Conversely,knockdown of miR-4458 with anti-miR-4458 significantly increased the protein levels of Lin28B,and promoted the cell proliferation,which could be reverted by knockdown of Lin28B expression.In addition,we detected the expression of Lin28B using RT-PCR in 40 human lung cancer tissues and matched peritumoral tissues,and found that Lin28B was overexpressed in lung cancer tissues and negatively correlated with miR-4458 expression (r=-0.694,P＜0.05).We conclude that miR-4458 is a tumor suppressor,and Lin28B is the direct target of miR-4458.These results suggest the modulation of miR-4458/Lin28B expression offers a potential therapeutic strategy for lung cancer.