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: Toshinaga Suto, Takehiko Yokobori, Reina Yajima, Hiroki Morita, Takaaki Fujii, Satoru Yamaguchi, Bolag Altan, Souichi Tsutsumi, Takayuki Asao, Hiroyuki Kuwano
• Journal: Carcinogenesis (Carcinogenesis) Vol. 36 Issue 3 Pg. 338-45 (Mar 2015) ISSN: 1460-2180 [Electronic] England
• PMID: 25503932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• 3' Untranslated Regions
• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• MIRN7 microRNA, human
• MicroRNAs
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• Proto-Oncogene Proteins c-raf
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Cetuximab

Topics

• 3' Untranslated Regions
• Antibodies, Monoclonal, Humanized (pharmacology)
• Biomarkers, Tumor (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cetuximab
• Colorectal Neoplasms (drug therapy, genetics, mortality, pathology)
• Drug Resistance, Neoplasm (genetics)
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-raf (genetics, metabolism)