Molecular Bases of Aberrant miR-182 Expression in Ovarian Cancer

Abstract

The molecular bases of miR-182 deregulation in epithelial ovarian cancers (EOCs) remain unknown and its diagnostic or prognostic role in EOCs is still unclear.

We performed miR-182 expression analysis using a microarray approach and real-time PCR (qPCR). We also used array comparative genomic hybridization and methylated DNA immunoprecipitation to study copy number changes and methylation aberrations within coding locus/promoter sequences of miR-182 in EOC tissues, respectively.

We have found that miR-182 expression is significantly increased in EOC (P<0.00001) and that higher miR-182 expression in EOC is linked with significantly shorter overall survival (P=0.026). The methylation of miR-182 promoter was significantly associated with lower miR-182 expression in EOC tissues (P=0.045). miR-182 over-expression is connected with copy number (CN) gains of this miRNA coding sequences in EOC (P=0.002), and the number of PRDM5 copies is significantly and inversely correlated with miR-182 expression evaluated by qPCR (R=-0.615, P=0.009). We conclude that the aberrant miR-182 expression in EOC may be due to CN gains within its coding locus. The miR-182 promoter is rarely methylated in EOC, and its methylation status is associated with lower miR-182 expression. Deletion of the PRDM5 locus may play a supportive role in miR-182 overexpression in EOC. miR-182 is an unfavorable prognostic factor in EOC. This article is protected by copyright. All rights reserved.

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