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Open AccessArticle

Epithelial-Mesenchymal Transition-Related MicroRNAs and Their Target Genes in Colorectal Cancerogenesis

University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1000 Ljubljana, Slovenia
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Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(10), 1603; https://doi.org/10.3390/jcm8101603
Received: 16 August 2019 / Revised: 26 September 2019 / Accepted: 27 September 2019 / Published: 3 October 2019
MicroRNAs of the miR-200 family have been shown experimentally to regulate epithelial-mesenchymal transition (EMT). Although EMT is the postulated mechanism of development and progression of colorectal cancer (CRC), there are still limited and controversial data on expression of miR-200 family and their target genes during CRC cancerogenesis. Our study included formalin-fixed paraffin-embedded biopsy samples of 40 patients (10 adenomas and 30 cases of CRC with corresponding normal mucosa). Expression of miR-141, miR-200a/b/c and miR-429 and their target genes (CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2) was analysed using quantitative real-time PCR. Expression of E-cadherin was analysed using immunohistochemistry. All miRNAs were down-regulated and their target genes showed the opposite expression in CRC compared to adenoma. Down-regulation of the miR-200 family at the invasive front in comparison to the central part of tumour was observed as well as a correlation of expression of miR-200b, CDKN1B, ONECUT2 and ZEB2 expression to nodal metastases. Expression of the miR-200 family and SOX2 also correlated with E-cadherin staining. These results suggest that the miR-200 family and their target genes contribute to progression of adenoma to CRC, invasive properties and development of metastases. Our results strongly support the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRC cancerogenesis. View Full-Text
Keywords: colorectal adenoma; colorectal carcinoma; metastases; intra-tumour heterogeneity; epithelial-mesenchymal transition; miR-200 family; target genes colorectal adenoma; colorectal carcinoma; metastases; intra-tumour heterogeneity; epithelial-mesenchymal transition; miR-200 family; target genes
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Ranković, B.; Zidar, N.; Žlajpah, M.; Boštjančič, E. Epithelial-Mesenchymal Transition-Related MicroRNAs and Their Target Genes in Colorectal Cancerogenesis. J. Clin. Med. 2019, 8, 1603.

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