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Sci Rep. 2014 Sep 1;4:6145. doi: 10.1038/srep06145.

MiR-198 represses tumor growth and metastasis in colorectal cancer by targeting fucosyl transferase 8.

Author information

1
1] State Key Laboratory for Oncogene and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China [2].
2
State Key Laboratory for Oncogene and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China.
3
Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

In this study we investigated the biological role and mechanism of miR-198 in colorectal carcinoma (CRC). MiR-198 expression was shown to exhibit a strongly negative correlation with lymph node invasion, distant metastasis and patient survival in examinations of colorectal cancer tissues and paired normal colorectal mucosa tissues. fucosyl transferase 8 (FUT8) was identified as a potential target of miR-198 in bioinformatics analysis and luciferase reporter assays. Overexpression of miR-198 in CRC cell lines decreased FUT8 levels as shown by immunofluorescence analysis, and inhibited cell proliferation, migration, and invasion. These anti-tumor phenotypes were rescued by reconstitution of FUT8 expression. Furthermore, miR-198 was shown to target the 3'UTR of FUT8 directly to downregulate FUT8 expression at both mRNA and protein levels in qRT-PCR and Western blot analyses, respectively. In vivo, restoration of miR-198 significantly inhibited xenograft growth and invasion of CRC tumors in nude mice. Therefore, it could be concluded that miR-198 suppresses the proliferation and invasion of CRC by directly targeting FUT8.

PMID:
25174450
PMCID:
PMC5385833
DOI:
10.1038/srep06145
[Indexed for MEDLINE]
Free PMC Article

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