Down-regulation of microRNA 10a expression in esophageal squamous cell carcinoma cells

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.