title: Down-regulation of microRNA 10a expression in esophageal squamous cell carcinoma cells.
abstract: This study identified significantly down-regulated microRNAs (miRs) specific for esophageal squamous cell carcinoma (ESCC) cells. Total RNA was extracted from ESCC cell lines (OE21 and TE10) and a non-malignant human esophageal squamous cell line (Het1A), and subjected to microarray analysis. Expression levels of miRs that showed significant down-regulation in ESCC cells compared to Het1A cells based on the comprehensive analysis were analyzed by quantitative reverse transcription polymerase chain reaction. Among the significantly down-regulated miRs, miR-10a expression levels in the five ESCC cell lines examined were significantly lower than in Het1A and the esophageal adenocarcinoma cells. Since miR-10a is a specific miR in ESCC, its clinical relevance was examined. Using ESCC tumor samples and non-cancerous tissue obtained endoscopically, the involvement of miR-10a in the clinicopathological findings was examined. MiR-10a expression was comparably down-regulated in the tumors of high-grade intraepithelial neoplasm and non-invasive ESCC, while the expression levels were elevated in the invasive ESCC tumors. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine, restored miR-10a expression in OE21 cells. Only a modest additive or synergistic effect was observed in the presence of a histone deacetylase inhibitor, trichostatin A. These results imply that miR-10a may be differentially expressed in ESCC cells and may be involved in ESCC development and progression. The unique epigenetic regulation of miR-10a expression can be mediated via hypermethylation of the CpG islands proximal to its gene locus, at least in certain ESCC cells.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki.
authors.forename: Naoki
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authors.lastname: Inoue
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authors.lastname: Matsushima
authors.forename: Tomayoshi
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authors.lastname: Hayashi
authors.forename: Masaki
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authors.forename: Shigekazu
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authors.lastname: Machida
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authors.lastname: Nanashima
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authors.lastname: Takeshima
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authors.lastname: Nakashima
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authors.lastname: Nagayasu
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authors.lastname: Yamashita
authors.forename: Kazuhiko
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authors.lastname: Nakao
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno