JOURNAL ARTICLE
MULTICENTER STUDY

Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma

María Ángeles Castilla, Gema Moreno-Bueno, Laura Romero-Pérez, Koen Van De Vijver, Michele Biscuola, María Ángeles López-García, Jaime Prat, Xavier Matías-Guiu, Amparo Cano, Esther Oliva, José Palacios
Journal of Pathology 2011, 223 (1): 72-80
21125666
Endometrial carcinosarcomas (ECSs) undergo a true epithelial-mesenchymal transition (EMT). The molecular determinants of the EMT in vivo are unclear, although a role for some miRNAs, mainly involving the miR-200 family, was recently suggested from in vitro cellular models. We analysed the microRNA (miRNA) signatures associated to EMT in human carcinosarcomas, and determined their relationships with EMT markers and repressors of E-cadherin transcription. The expression of E-, P- and N-cadherin, cadherin-11, p120, vimentin, SPARC, fascin and caveolin-1 was studied in a group of 76 ECS by immunohistochemistry. In addition, real-time PCR was used to measure the differences in the expression of 384 miRNAs, E-cadherin, cadherin-11, SPARC, SNAIL, ZEB1, ZEB2, TWIST-1, TCF4, TGFβ1 and TGFβ2 between the epithelial and mesenchymal components of 23 ECSs. A loss of epithelial characteristics, including cadherin switching and the acquisition of a mesenchymal phenotype, was accompanied by changes in the profile of miRNA expression and the up-regulation of all the E-cadherin repressors analysed. A greater than five-fold difference in the expression of 14 miRNAs between both neoplastic components was seen. Members of the miR-200 family were down-regulated in the mesenchymal part of the ECS. In addition, miR-23b and miR-29c, which are involved in the inhibition of mesenchymal markers, and miR-203, which is involved in the inhibition of cell stemness, were also down-regulated. Up-regulated miRNAs included miR-155, miR-369-5p, miR-370, miR-450a and miR-542-5p. These data suggest that in human ECS, the interplay between transcriptional repressors of E-cadherin and miRNAs provides a link between EMT-activation and the maintenance of stemness.

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