微小RNA-497通过抑制Nrdp1促进结肠癌细胞转移。

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

作者信息

Jiang Yongsheng, Meng Qinghua, Qi Jiaqin, Shen Haiyu, Sun Shaochuan

机构信息

Department of General Surgery, Jinan Central Hospital of Shandong University, 105 Jiefang Road, Lixia District, Jinan, 250013, China.

出版信息

Tumour Biol. 2015 Sep;36(10):7641-7. doi: 10.1007/s13277-015-3489-9. Epub 2015 Apr 30.

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.

摘要

我们最近发现,Nrdp1可抑制结肠直肠癌(CRC)细胞中ErB3的磷酸化,从而抑制表皮生长因子受体(EGFR)信号刺激的MMP7激活,以促进CRC转移。在本研究中,我们检测了CRC细胞中Nrdp1的调控机制。与配对的正常结直肠组织相比,我们在CRC标本中检测到miR-497显著增加。此外,我们检测到miR-497水平与Nrdp1水平之间呈强正相关,而miR-497水平与MMP7水平之间呈强负相关。在体外,人CRC细胞中miR-497的过表达显著降低了Nrdp1的转录本和蛋白质水平,反之亦然。此外,人CRC细胞中miR-497的过表达还显著增加了MMP7的转录本、细胞蛋白和分泌蛋白,导致在transwell细胞迁移试验中细胞侵袭性增加。此外,我们发现MiR-497直接靶向Nrdp1 mRNA的3'-UTR以抑制其翻译。总之,我们的数据表明,CRC细胞中Nrdp1对MMP7的调控可能被miR-497通过抑制Nrdp1翻译所抑制。因此,我们的工作突出了一种调节CRC转移的新型分子调控机制。

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