MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells
Open Access
- 22 March 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Translational Medicine
- Vol. 9 (1), 30
- https://doi.org/10.1186/1479-5876-9-30
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.Keywords
This publication has 43 references indexed in Scilit:
- Biomarkers of response to therapy in oesophago-gastric cancerGut, 2008
- MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epitheliaProceedings of the National Academy of Sciences of the United States of America, 2008
- Regulation of microRNA processing in development, differentiation and cancerJournal of Cellular and Molecular Medicine, 2008
- MicroRNAs as regulators of epithelial-mesenchymal transitionCell Cycle, 2008
- The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2Journal of Biological Chemistry, 2008
- The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1Nature, 2008
- MicroRNAs accurately identify cancer tissue originNature Biotechnology, 2008
- Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell CarcinomaCancer Research, 2008
- The transcription factor ZEB1 (δEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarityOncogene, 2007
- Epithelial-mesenchymal and mesenchymal-epithelial transitions during cancer progression.2007