RRC ID 38480
Author Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, Hayashi T, Kunizaki M, Hidaka S, Nagayasu T, Nakashima M, Ujifuku K, Mitsutake N, Ohtsuru A, Yamashita S, Korpal M, Kang Y, Gregory PA, Goodall GJ, Kohno S, Nakao K.
Title MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells.
Journal J Transl Med
Abstract BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC.
METHODS:Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR.
RESULTS:Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC.
CONCLUSIONS:These results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.
Volume 9
Pages 30
Published 2011-3-22
DOI 10.1186/1479-5876-9-30
PII 1479-5876-9-30
PMID 21426561
PMC PMC3076245
MeSH Apoptosis / genetics Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Differentiation / genetics Cell Line, Tumor Cell Movement / genetics* Cell Proliferation Epithelial-Mesenchymal Transition / genetics Esophageal Neoplasms / genetics* Esophageal Neoplasms / pathology* Gene Expression Profiling Gene Expression Regulation, Neoplastic* Homeodomain Proteins / genetics* Homeodomain Proteins / metabolism Humans MicroRNAs / genetics MicroRNAs / metabolism* Neoplasm Invasiveness Phenotype Repressor Proteins / genetics* Repressor Proteins / metabolism Up-Regulation / genetics Zinc Finger E-box Binding Homeobox 2
IF 4.124
Times Cited 102
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL
Resource
Human and Animal Cells TE-5(RCB1949) TE-8(RCB2098) TE-10(RCB2099) TE-11(RCB2100)