Ran Ni, Yongjie Huang, Jing Wang

Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression patterns and cancer development. Abnormally expressed miRNA-98 (miR-98) was found in certain types of human cancers. The biological roles of miR-98 in lung cancer, however, remain largely undefined. We evaluated the expression of miR-98 in normal lung tissues, lung cancer tissues, normal human bronchial epithelial cells, and lung cancer cells using quantitative real-time polymerase chain reaction. Effect of miR-98 on proliferation of lung cancer cells was investigated using MTT assay and colony formation assay. Transwell assay was used to assess the effects of miR-98 on migration and invasion of lung cancer cells. Whether miR-98 targets the 3'-untranslated region (3'-UTR) of integrin β3 (ITGB3) coding gene ITGB3 mRNA was ascertained using luciferase reporter assay. Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth in vivo. We confirmed that miR-98 was frequently low expressed in lung cancer tissues and human lung cancer cells. Reintroduction of miR-98 into lung cancer cells inhibited cell proliferation, migration, and invasion in vitro and suppressed tumor formation in a nude mouse model. Furthermore, we identified that miR-98 exerted inhibitory roles by directly binding to 3'-UTR of ITGB3 mRNA, thus negatively regulated the expression of ITGB3. Interestingly, upon restoring the expression of ITGB3, the effect of miR-98 on cell proliferation was partially reversed. Our findings suggest that miR-98 prevents proliferation, migration, and invasion of lung cancer cells by directly binding to the 3'-UTR of ITGB3 mRNA and could be a promising treatment option in anticancer therapy.