MiR-132 upregulation promotes gastric cancer cell growth through suppression of FoxO1 translation.

Abstract

Gastric carcinoma (GC) is a prevalent malignant cancer worldwide and is highly lethal due to its fast growth. Hence, treatments to suppress GC cell growth may be applied together with surgery and chemotherapy to increase therapeutic outcome. Previous studies have shown the involvement of some microRNAs (miRNAs or miRs) in the carcinogenesis of GC, whereas a role of miR-132 in regulating the growth of GC has not been reported. Here, we report that overexpression of miR-132 in GC cells decreased FoxO1 protein levels, whereas depletion of miR-132 increased FoxO1 protein levels, without altering FoxO1 transcripts. Bioinformatics analyses showed that miR-132 bound to 3'-untranslated region (3'-UTR) of FoxO1 messenger RNA (mRNA) to prevent its translation, which was confirmed by luciferase reporter assay. Moreover, miR-132-mediated suppression of FoxO1 in GC cells resulted in a significant increase in GC cell growth in vitro and in vivo, while increases in FoxO1 by expression of antisense of miR-132 significantly decreased GC cell growth in vitro and in vivo. Finally, miR-132 levels were found significantly increased in GC specimens, compared to those in paired non-tumor gastric tissue. Together, our data suggest that miR-132 upregulation in GC cells may promote cell growth through suppression of FoxO1 translation.