MicroRNA-223 regulates FOXO1 expression and cell proliferation

In HCT116 colorectal cancer cells, HeLa cervical cancer cells and HuH-7 hepatoma cells, miR-223 is expressed at a low level. Through infection with lentivirus containing miR-223 precursor, miR-233 was overexpressed in all these cells. Interestingly, the expression levels of FOXO1 mRNA and protein, and phosphorylation levels became significantly lower than those of their control. FOXO1 was down-regulated mainly in the cytoplasm, while the nuclear FOXO1 level became relatively high compared to the cytoplasm. As the unphosphorylated active form of FOXO1 increased in the cells, cyclin D1/p21/p27 were up-regulated at either mRNA or protein level. Proliferation of the cells was also greatly inhibited when miR-223 was over-expressed. Therein, our data suggest that miR-223 regulates FOXO1 expression and cell proliferation.

► Informatics screen shows miR-223 binding to FOXO1 mRNA 3′UTR. ► Reporter assay identified that FOXO1 was targeted by miR-223. ► Overexpression of miR-223 resulted in down-regulation of cytoplasmic FOXO1. ► FOXO1 phosphorylation was inhibited and the nuclear FOXO1 was accumulated. ► With the regulation of p21, p27 and cyclin D1, cell proliferation was suppressed.