MicroRNA-4458 suppresses the proliferation of human lung cancer cells in vitro by directly targeting Lin28B

• 来源期刊: 中国药理学报（英文版）
• 关键词: lung cancer A549 cells NCl-H1299 cells miR-4458 Lin28B cell proliferation
• 年，卷（期）: 2017,（9）
• 页码范围: 1297-1304
• 页数: 8页
• 语种: 英文
• DOI: 10.1038/aps.2017.73

摘要

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.