Global microRNA expression profiles in endometrioid endometrial carcinoma in Hong Kong women Free

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Introduction. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression by inducing cleavage of the targeted messenger or by inhibiting translation, and involved in a wide range of basic biological processes such as cell proliferation, development, apoptosis and stress response. Endometrial cancer is the third most common gynaecologic malignancy in Hong Kong and about 80-90 % are endometrioid endometrial adenocarcinomas (EEC). This study was to investigate miRNAs in EEC in Hong Kong women.

Methods. We examined the expression of 156 mature miRNAs by high through-put real-time RT-PCR assays in 13 laser capture microdissected EEC including 4 advanced- and 9 early-stage tumors, and compared that to 5 normal counterparts. We used dChip program for the data analysis.
 >Results. Unsupervised hierarchical clustering analysis of these global miRNA expression profiles showed a distinct separation between cancers and normal controls.Supervised clustering analysis identified 13 miRNAs up-regulated and 3 miRNAs down-regulated, respectively, in EEC. The fold-change observed in cancer in relation to normal controls varied between 2.3 and 42.5-fold up-regulation and between -2.63 and -5.30-fold down-regulation. In addition, when the miRNA expression profiles in advanced stage tumors were compared to those in early stage tumors, 5 miRNAs were significantly over-expressed and one miRNA under-expressed in advanced stage tumors. We further searched the predicted target genes of these miRNAs on three databases including http://www.microrna.org, http://www.sanger.ac.uk, and http://pictar.bio.nyu.edu. A total of 39 aberrantly regulated genes that were previously identified by us in a large set of ECC, were predicted as the target genes of 8 miRNAs of most interest in ECC.
 >Conclusion. To the best of our knowledge, this is the first report demonstrating miRNA dysregulation as a key event in endometrial cell transformation. Unique miRNA signatures, novel molecular markers and candidate therapeutic targets may be further identified in expanded study of miRNA expression profiling and functional role of miRNAs in EEC.