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- Title
MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation.
- Authors
Suto, Toshinaga; Yokobori, Takehiko; Yajima, Reina; Morita, Hiroki; Fujii, Takaaki; Yamaguchi, Satoru; Altan, Bolag; Tsutsumi, Souichi; Asao, Takayuki; Kuwano, Hiroyuki
- Abstract
Our data suggest that miR-7 directly targets EGFR. miR-7 powerfully suppressed the proliferation of colorectal cancer cells, and the growth inhibitory effect was enhanced by cetuximab, a monoclonal antibody against EGF.MicroRNA-7 (miR-7) has been reported to be a tumor suppressor in all malignancies including colorectal cancer (CRC). However, its significance for CRC clinical outcomes has not yet been explored. The potential for miR-7 to act as a tumor suppressor by coordinately regulating the epidermal growth factor receptor (EGFR) signaling pathway at several levels was examined. We investigated the tumor inhibitory effect of miR-7 in CRC, with particular focus on the relationship between miR-7 and the EGFR pathway. Quantitative reverse transcription–PCR was used to evaluate miR-7 expression in 105 CRC cases to determine the clinicopathologic significance of this miRNA. The regulation of EGFR by miR-7 was examined with miR-7 precursor-transfected cells. Furthermore, we investigated whether miR-7 suppresses proliferation of CRC cells in combination with cetuximab, a monoclonal antibody against EGFR. Multivariate analysis indicated that low miR-7 expression was an independent prognostic factor for poor survival (P = 0.0430). In vitro assays showed that EGFR and RAF-1 are direct targets of miR-7, which potently suppressed the proliferation of CRC cells, and, interestingly, that the growth inhibitory effect of each of these was enhanced by cetuximab. miR-7 is a meaningful prognostic marker. Furthermore, these data indicate that miR-7 precursor, alone or in combination with cetuximab, may be useful in therapy against CRC.
- Subjects
MICRORNA; GENE expression; COLON cancer prognosis; CETUXIMAB; EPIDERMAL growth factor receptors regulation; CANCER cell proliferation
- Publication
Carcinogenesis, 2015, Vol 36, Issue 3, p338
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgu242