title: MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation.
abstract: 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.
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Suto
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan bori45@gunma-u.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Yajima
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Bolag
authors.initials: B
authors.lastname: Altan
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D020413:3' Untranslated Regions; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors; D035683:MicroRNAs; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; C549242:MIRN7-1 microRNA, human; C512478:EGFR protein, human; C535150:MAPK1 protein, human