title: MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishida
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Shibata
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D008297:Male; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D000068878:Trastuzumab