RRC ID 36878
Author Sakimura S, Sugimachi K, Kurashige J, Ueda M, Hirata H, Nambara S, Komatsu H, Saito T, Takano Y, Uchi R, Sakimura E, Shinden Y, Iguchi T, Eguchi H, Oba Y, Hoka S, Mimori K.
Title The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer.
Journal Ann. Surg. Oncol.
Abstract BACKGROUND:MicroRNAs have roles in the regulation of the epithelial-mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer.
METHODS:In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3' untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines.
RESULTS:Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3'UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells.
CONCLUSIONS:The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.
Volume 22 Suppl 3
Pages S1436-43
Published 2015-12
DOI 10.1245/s10434-015-4418-2
PII 10.1245/s10434-015-4418-2
PMID 25707493
MeSH Aged Apoptosis Biomarkers, Tumor / genetics* Biomarkers, Tumor / metabolism Blotting, Western Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition / genetics* Female Gene Expression Regulation, Neoplastic* Humans Immunoenzyme Techniques Lymphatic Metastasis Male MicroRNAs / genetics* Neoplasm Grading Neoplasm Invasiveness Neoplasm Staging Prognosis RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Snail Family Transcription Factors Stomach Neoplasms / genetics Stomach Neoplasms / pathology* Survival Rate Transcription Factors / genetics Transcription Factors / metabolism* Tumor Cells, Cultured
IF 3.681
Times Cited 15
Human and Animal Cells MKN7(RCB0999) MKN45(RCB1001)