MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor

MicroRNAs (miRNAs), which are noncoding RNAs that regulate gene expression, are involved in tumor metastasis. In this study, we describe the down-regulation and function of miR-139 in colorectal cancer (CRC) metastasis. MiR-139 was found underexpressed in 34 CRC tissues compared to their corresponding nontumor tissues. Decreased miR-139 in CRC tissue was associated with disease progression and metastasis. Re-expression of miR-139 did not inhibit CRC cell growth but suppresses CRC cell metastasis and invasion in vitro and in vivo. MiR-139 might suppress CRC cells invasion and metastasis by targeting type I insulin-like growth factor receptor (IGF-IR). We also found miR-139 directed migration inactivation of human CRC cells involves down-regulation of matrix metalloproteinase 2 (MMP-2). The IGF-IR/MEK/ERK signaling was inhibited by miR-139 overexpression and then resulted in MMP-2 promoter suppression. Taken together, our results provide evidence that miR-139 might function as a metastasis suppressor in CRC. Targeting miR-139 may provide a strategy for blocking CRC metastasis. (C) 2012 Elsevier Inc. All rights reserved.