MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28
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Jian Wang1,2,*, Hai Li3,*, Yong Wang1,2, Libin Wang2, Xiurui Yan2, Dong Zhang3, Xiaoqiang Ma3, Yong Du1, Xiaoming Liu2, Yinxue Yang1,2,3
1The general hospital, Ningxia Medical University, Yinchuan 750004, China
2Human Stem Cell Institute of the General Hospital at Ningxia Medical University, Yinchuan 750004, China
3Department of Colorectal Surgery, the General Hospital of Ningxia Medical University, Yinchuan 750004, China
*These authors contributed equally to this work
Yinxue Yang, email: [email protected]
Xiaoming Liu, email: [email protected], [email protected]
Keywords: microRNAs, colorectal cancer, miR-552, antagomir, ADAM28
Received: January 25, 2016 Accepted: August 08, 2016 Published: September 21, 2016
Colorectal cancer (CRC) is one of the most common prevalent cancer types worldwide. MicroRNAs (miRNAs or miRs) have been demonstrated to play crucial roles in the development, metastasis and drug resistance of CRC. In the present study, a strikingly elevated expression of miR-552 was determined in CRC tumor tissues and cells by a miRNA profiling analysis. Importantly, the gene of A Disintegrin And Metalloprotease (ADAM) family member 28 (ADAM28) was identified as a target of miR-552, which was further validated in terms of genetic dual luciferase report assay. Furthermore, an inhibition of miR-552 in LOVE and LS174T CRC cells by transducing miR-552 inhibitor (antagomiR-552) with a lentiviral vector exhibited an ability to reduce cell proliferation, migration and clonogenicity. Moreover, both LOVO and LS174T cells stably expressing miR-552 inhibitor displayed a decreased ability to develop tumors in a murine xenograft model in vivo. In contrast, a knockdown of ADAM28 by short hairpin RNA could reverse the antagomiR-552-induced inhibition of metastatic features of CRC cells in vitro. These results suggested that miR-552 is an oncomir able to promote CRC metastasis in part through a mechanism of targeting ADAM28, which may be a novel target for CRC treatment and warrants for further investigation.
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