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  • Title: MiR-497 promotes metastasis of colorectal cancer cells through Nrdp1 inhibition.
    Author: Jiang Y, Meng Q, Qi J, Shen H, Sun S.
    Journal: Tumour Biol; 2015 Sep; 36(10):7641-7. PubMed ID: 25926384.
    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.
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