MicroRNA-223 regulates FOXO1 expression and cell proliferation

• Published in: FEBS letters 2012-04, Vol.586 (7), p.1038-1043
• Main Authors: Wu, Lihui, Li, Huihui, Jia, Cheng You, Cheng, Wei, Yu, Mei, Peng, Min, Zhu, Yuanqing, Zhao, Qianlei, Dong, Yi Wei, Shao, Kang, Wu, Anle, Wu, Xing Zhong
• Format: Article
• Language: English
• Subjects: Cell Line, Transformed; Cell Line, Tumor; Cell Nucleus - metabolism; Cell Proliferation; Colorectal Neoplasms - metabolism; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor Proteins - genetics; Cyclin-Dependent Kinase Inhibitor Proteins - metabolism; Cytoplasm - metabolism; Female; Forkhead Box Protein O1; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; FOXO1; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms - metabolism; Male; MicroRNA-223; MicroRNAs - biosynthesis; MicroRNAs - genetics; MicroRNAs - physiology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasms - metabolism; Phosphorylation; Protein Processing, Post-Translational; Protein Transport; RNA, Messenger - genetics; RNA, Messenger - metabolism; Uterine Cervical Neoplasms - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.02.050

► 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. 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.