MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells

Objectives: MicroRNAs (miRNAs) are small functional RNAs that regulate mRNAs for degradation or translational suppression. In the present study, we aimed to reveal functional importance of miRNA-494 (miR-494) in A549 human lung cancer cells. Materials and methods: We established A549 cells that constitutively expressed miR-494. Next, we sought to investigate insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) mRNA as an miR-494 target. For this, we constructed a reporter plasmid bearing potential miR-494 binding sequences derived from the 3'-untranslated region (3'-UTR) of IGF2BP1 mRNA in the 3'-UTR of the luciferase gene. Results: Through comparison between miR-494 expressing cells and control cells, we revealed that miR-494 suppressed cell proliferation and colony forming activity, and induced senescence. Reporter activity was inhibited by miR-494. In addition, IGF2BP1 mRNA levels were down-regulated in A549 cells that constitutively expressed miR-494. IGF2BP1 has been shown to bind and suppress IGF2 mRNA, and this could be a reason why IGF2BP1 can regulate cell function. Therefore, we analysed IGF2 mRNA levels and revealed that IGF2 was up-regulated in A549 cells that constitutively expressed miR-494. Finally, elevated IGF2 mRNA levels in A549 cells that constitutively expressed miR-494 were suppressed to basal level by an miR-494 inhibitor. Conclusions: Taken together, IGF2BP1 and its downstream target IGF2 could be a crucial axis for miR-494 in regulation of the destiny of A549 cells.