Naohiro Nishida 1 , Koshi Mimori , Muller Fabbri , Takehiko Yokobori , Tomoya Sudo , Fumiaki Tanaka , Kohei Shibata , Hideshi Ishii , Yuichiro Doki , Masaki Mori Show Affiliations »
Abstract
PURPOSE: MicroRNA 125a-5p (miR-125a-5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary, lung, and central nervous system. However, the clinical significance of miR-125a-5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a-5p in gastric cancer, focusing in particular on the miR-125a-ERBB2 (HER2, HER-2/neu) pathway. EXPERIMENTAL DESIGN: Quantitative RT-PCR was used to evaluate miR-125a-5p expression in 87 gastric cancer cases to determine the clinicopathologic significance of miR-125a-5p expression. The regulation of ERBB2 by miR-125a-5p was examined with precursor miR-125a-transfected cells. Furthermore, we investigated whether miR-125a-5p suppresses proliferation of gastric cancer cells in combination with trastuzumab, a monoclonal antibody against ERBB2. RESULTS: Low expression levels of miR-125a-5p were associated with enhanced malignant potential such as tumor size (P = 0.0068), tumor invasion (P = 0.031), liver metastasis (P = 0.029), and poor prognosis (P = 0.0069). Multivariate analysis indicated that low miR-125a-5p expression was an independent prognostic factor for survival. In vitro assays showed that ERBB2 is a direct target of miR-125a-5p, which potently suppressed the proliferation of gastric cancer cells, and, interestingly, the growth inhibitory effect was enhanced in combination with trastuzumab. CONCLUSIONS: miR-125a-5p is a meaningful prognostic marker. Furthermore, miR-125a-5p mimic alone or in combination with trastuzumab could be a novel therapeutic approach against gastric cancer. ©2011 AACR.
PURPOSE: MicroRNA 125a-5p (miR-125a -5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary , lung, and central nervous system. However, the clinical significance of miR-125a -5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a -5p in gastric cancer , focusing in particular on the miR-125a -ERBB2 (HER2 , HER-2/neu ) pathway. EXPERIMENTAL DESIGN: Quantitative RT-PCR was used to evaluate miR-125a -5p expression in 87 gastric cancer cases to determine the clinicopathologic significance of miR-125a -5p expression. The regulation of ERBB2 by miR-125a -5p was examined with precursor miR-125a -transfected cells. Furthermore, we investigated whether miR-125a -5p suppresses proliferation of gastric cancer cells in combination with trastuzumab , a monoclonal antibody against ERBB2 . RESULTS: Low expression levels of miR-125a -5p were associated with enhanced malignant potential such as tumor size (P = 0.0068), tumor invasion (P = 0.031), liver metastasis (P = 0.029), and poor prognosis (P = 0.0069). Multivariate analysis indicated that low miR-125a -5p expression was an independent prognostic factor for survival. In vitro assays showed that ERBB2 is a direct target of miR-125a -5p, which potently suppressed the proliferation of gastric cancer cells, and, interestingly, the growth inhibitory effect was enhanced in combination with trastuzumab . CONCLUSIONS: miR-125a -5p is a meaningful prognostic marker. Furthermore, miR-125a -5p mimic alone or in combination with trastuzumab could be a novel therapeutic approach against gastric cancer . ©2011 AACR.
Entities: Chemical
Disease
Gene
Species
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Year: 2011
PMID： 21220473 DOI： 10.1158/1078-0432.CCR-10-2132
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531