Down-regulation of miR-145 and miR-143 might be associated with DNA methyltransferase 3B overexpression and worse prognosis in endometrioid carcinomas

SummaryThe aim of this study was to determine the clinicopathologic significance of miR-145 and miR-143 down-regulation in endometrial cancers. The microRNA profiles were analyzed by microRNA microarray. The expression levels of miR-145 and miR-143 in 73 endometrial cancers were further determined by quantitative real-time polymerase chain reaction. Potential targets of miR-145/143 were defined. The status of DNA methyltransferase 3B (DNMT3B), mutL homologs 1, and phosphatase and tensin homolog was assessed using immunohistochemistry. miR-145 and miR-143 frequently co-down-regulated in endometrial cancers, but the expression levels varied greatly between endometrioid carcinomas (ECs) and non-ECs (NECs); they were significantly lower in ECs than in NECs (P < .05). DNMT3B was defined as a potential target of miR-145/143 by Internet algorithms. In ECs, DNMT3B overexpression occurred more often in the miR-145 and miR-143 down-regulation subgroups, and the correlation between DNMT3B and miR-145 status reached statistical significance (P = .021), whereas such phenomena were not present in NECs (P > .05). In univariate analysis, the combination of DNMT3B overexpression and miR-145 or miR-143 down-regulation was more powerful in predicting shorter survival (P < .05) than use of the biomarkers individually (P > .05). In multivariate analysis, such combination was not an independent predictor of disease-free survival (P > .05). Our findings suggest that the target and function of miR-145 and miR-143 may differ in ECs versus NECs. DNMT3B might be a potential target of miR-145 and miR-143 in ECs. Furthermore, the combined miR-145 or miR-143 and DNMT3B status may have a prognostic impact on ECs.