Epithelial-mesenchymal transition-related microRNAs and their target genes in colorectal cancerogenesis

Ranković, Branislava (author), Zidar, Nina (author), Žlajpah, Margareta (author), Boštjančič, Emanuela (author)

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.

• Language: English
• Keywords: colorectal adenoma, colorectal carcinoma, metastases, intra-tumour heterogeneity, epithelial-mesenchymal transition, miR-200 family, target genes
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: 21 str.
• Numbering: Vol. 8, iss. 10, art. 1603
• PID: 20.500.12556/RUL-128788
• UDC: 616-006
• ISSN on article: 2077-0383
• DOI: 10.3390/jcm8101603
• COBISS.SI-ID: 34547929
• Publication date in RUL: 29.07.2021

Record is a part of a journal

• Title: Journal of clinical medicine
• Shortened title: J. clin. med.
• Publisher: MDPI
• ISSN: 2077-0383
• COBISS.SI-ID: 5405759

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 03.10.2019

Secondary language

• Language: Slovenian
• Keywords: kolorektalni adenom, kolorektalni karcinom, metastaze, intra-tumorska heterogenost, epitelno-mezenhimska tranzicija, družina miR-200, tarčni geni

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J3-1754
• Name: Novi prognostični in diagnostični označevalci v razvoju raka debelega črevesa in danke

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0054
• Name: Patologija in molekularna genetika