miR-487a promotes progression of gastric cancer by targeting TIA1.

ABSTRACT

Gastric cancer (GC) is one of the most common malignancies as well as the third leading cause for cancer-related death. Molecular basis of GC are essential and critical for its therapeutic treatment, but still remain poorly understood. T-cell intracellular antigen-1 (TIA1) extensively involves in cancer progression, whereas its role and regulation mechanism in GC have not been revealed. In the present study, we found that TIA-1 protein level was down-regulated in GC tissues and TIA1 inhibited proliferation and promoted apoptosis of GC cells. Then, we used bioinformatics to predict miR-487a as the upstream regulator of TIA1 and we also observed an inverse correlation between miR-487a level and TIA-1 protein level in GC tissues. Next, we demonstrated that miR-487a directly targeted TIA1 via binding to its 3'-untranslated region. Furthermore, we investigated the role of miR-487a-TIA1 pathway in the growth of GC cells both in vitro and in vivo. The repression of TIA-1 by miR-487a promoted cell proliferation and suppressed cell apoptosis in vitro, and the knockdown of miR-487a had the opposite effects. Finally, we demonstrated that miR-487a promoted the development of gastric tumor growth in xenograft mice by targeting TIA-1. These effects could be partially reversed by restoring the expression of TIA-1. Overall, our results reveal that TIA1 is a tumor suppressor gene and is directly regulated by miR-487a in GC, which may offer new therapeutic targets for GC treatment.