MiR‐339 depresses cell proliferation via directly targeting S‐phase kinase‐associated protein?2 mRNA in lung cancer

摘要

Background S‐phase kinase‐associated protein?2 (Skp2) takes great part in the development of multiple tumors. However, the post‐transcriptional modulation mechanism of Skp2 remains unclear. Here, we present a new regulatory microRNA of Skp2, miR‐339, which directly targets Skp2 to inhibit cell proliferation in lung cancer. Methods The expression of miR‐339 or Skp2 in lung cancer samples was tested by real time‐PCR. The correlation between miR‐339 and Skp2 in lung cancer samples was analyzed by Pearson's correlation coefficient. The effect of miR‐339 or anti‐miR‐339 on Skp2 was evaluated by immunoblotting. The luciferase reporter gene assay was used to test the targeting of miR‐339 on Skp2. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5 diphenyltetrazolium bromide and colony formation analysis were applied to examine the function of miR‐339 targeting Skp2 in lung cancer cells. Results The negative correlation of miR‐339 with Skp2 was found in clinical human lung cancer tissues. Furthermore, Skp2 expression was obviously abated by miR‐339 in lung cancer A549 cells. Mechanistically, we used bioinformatics to predict that miR‐339 could target the 3′‐untranslated region of Skp2 mRNA. Luciferase reporter gene assay demonstrated that miR‐339 could decrease the luciferase activities of the 3′‐untranslated region vector of Skp2. In terms of function, ectopic miR‐339 expression significantly suppressed cell proliferation in lung cancer. Overexpressed Skp2 accelerated miR‐339‐bated proliferation of lung cancer cells. MiR‐339 inhibitor promoted cell proliferation in lung cancer, but Skp2 RNA interference reversed miR‐339 inhibitor‐driven cell proliferation. Conclusion MiR‐339 targets the 3′‐untranslated region of Skp2 mRNA to depress the proliferation of lung cancer cells.