MiR-497 promotes metastasis of colorectal cancer cells through Nrdp1 inhibition

Abstract

We have recently shown that Nrdp1 inhibits phosphorylation of ErB3 in colorectal cancer (CRC) cells, to suppress epidermal growth factor receptor (EGFR) signaling-stimulated MMP7 activation for CRC metastasis. In this study, we examined the control of Nrdp1 in CRC cells. We detected significant increases in miR-497 in CRC specimen, compared to paired normal colorectal tissue. Moreover, we detected a strong positive correlation between miR-497 levels and Nrdp1 levels, and a strong inverse correlation between miR-497 levels and MMP7 levels. In vitro, overexpression of miR-497 in human CRC cells significantly decreased Nrdp1 transcripts and protein, and vice versa. Moreover, overexpression of miR-497 in human CRC cells also significantly increased MMP7 transcripts, cellular protein, and secreted protein, resulting in increases in cell invasiveness in a transwell cell migration assay. Furthermore, we found that MiR-497 directly targeted 3'-UTR of Nrdp1 mRNA to inhibit its translation. Together, our data suggest that the regulation of MMP7 by Nrdp1 in CRC cells could be inhibited by miR-497 through suppressing Nrdp1 translation. Our work thus highlights a novel molecular regulatory machinery that regulates metastasis of CRC.

Keywords: Colorectal cancer (CRC); MMP7; Neuregulin receptor degradation protein-1 (Nrdp1); miR-497.