Cargando…

MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer

BACKGROUND: Invasion of the surrounding tissue is part of the metastatic cascade. Here, we examined the invasion of pancreatic ductal adenocarcinoma (PDAC) cells into the mesothelial barrier and identified the related microRNA (miRNA) expression profiles. METHODS: The interactions between PDAC cells...

Descripción completa

Detalles Bibliográficos
Autores principales: Listing, H, Mardin, W A, Wohlfromm, S, Mees, S T, Haier, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453619/
https://www.ncbi.nlm.nih.gov/pubmed/25422915
http://dx.doi.org/10.1038/bjc.2014.587
_version_ 1782374486761275392
author Listing, H
Mardin, W A
Wohlfromm, S
Mees, S T
Haier, J
author_facet Listing, H
Mardin, W A
Wohlfromm, S
Mees, S T
Haier, J
author_sort Listing, H
collection PubMed
description BACKGROUND: Invasion of the surrounding tissue is part of the metastatic cascade. Here, we examined the invasion of pancreatic ductal adenocarcinoma (PDAC) cells into the mesothelial barrier and identified the related microRNA (miRNA) expression profiles. METHODS: The interactions between PDAC cells and mesothelial monolayers were characterised and quantified using a specific time-lapse videomicroscopy assay. Pancreatic ductal adenocarcinoma cells were further evaluated using the adhesion assay, and miRNA, mRNA and protein expressions were determined using microarray, q-RT–PCR and western blots, respectively. These data were correlated with in vivo dissemination scores. RESULTS: Two groups of PDAC cell lines were distinguished by their integration capacity into the mesothelial monolayer using mean elongation factors (MEFs). Adhesion assays showed a concordant relation between adhesive properties and integration capacity. The distant metastases scores were reverse correlated with MEFs. Microarray analysis of these groups revealed that miR-23a and/or miR-24 target for FZD5, HNF1B and/or TMEM92, respectively, and that they are significantly deregulated. CONCLUSIONS: MiR-23a and/or miR-24 overexpression leads to gene silencing of FZD5, TMEM92 and/or HNF1B. Their downregulation induces deregulated expression and degradation of E-cadherin and β-catenin causing destabilisation of the cadherin/catenin complex, and altered the expression of Wnt-related genes. We propose a molecular (epi)genetic mechanism by which increased EMT-like cell shape transformation and integration into mesothelial monolayers of PDAC cells can be observed.
format Online
Article
Text
id pubmed-4453619
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-44536192016-01-06 MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer Listing, H Mardin, W A Wohlfromm, S Mees, S T Haier, J Br J Cancer Molecular Diagnostics BACKGROUND: Invasion of the surrounding tissue is part of the metastatic cascade. Here, we examined the invasion of pancreatic ductal adenocarcinoma (PDAC) cells into the mesothelial barrier and identified the related microRNA (miRNA) expression profiles. METHODS: The interactions between PDAC cells and mesothelial monolayers were characterised and quantified using a specific time-lapse videomicroscopy assay. Pancreatic ductal adenocarcinoma cells were further evaluated using the adhesion assay, and miRNA, mRNA and protein expressions were determined using microarray, q-RT–PCR and western blots, respectively. These data were correlated with in vivo dissemination scores. RESULTS: Two groups of PDAC cell lines were distinguished by their integration capacity into the mesothelial monolayer using mean elongation factors (MEFs). Adhesion assays showed a concordant relation between adhesive properties and integration capacity. The distant metastases scores were reverse correlated with MEFs. Microarray analysis of these groups revealed that miR-23a and/or miR-24 target for FZD5, HNF1B and/or TMEM92, respectively, and that they are significantly deregulated. CONCLUSIONS: MiR-23a and/or miR-24 overexpression leads to gene silencing of FZD5, TMEM92 and/or HNF1B. Their downregulation induces deregulated expression and degradation of E-cadherin and β-catenin causing destabilisation of the cadherin/catenin complex, and altered the expression of Wnt-related genes. We propose a molecular (epi)genetic mechanism by which increased EMT-like cell shape transformation and integration into mesothelial monolayers of PDAC cells can be observed. Nature Publishing Group 2015-01-06 2014-11-25 /pmc/articles/PMC4453619/ /pubmed/25422915 http://dx.doi.org/10.1038/bjc.2014.587 Text en Copyright © 2015 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Listing, H
Mardin, W A
Wohlfromm, S
Mees, S T
Haier, J
MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
title MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
title_full MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
title_fullStr MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
title_full_unstemmed MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
title_short MiR-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
title_sort mir-23a/-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453619/
https://www.ncbi.nlm.nih.gov/pubmed/25422915
http://dx.doi.org/10.1038/bjc.2014.587
work_keys_str_mv AT listingh mir23a24inducedgenesilencingresultsinmesothelialcellintegrationofpancreaticcancer
AT mardinwa mir23a24inducedgenesilencingresultsinmesothelialcellintegrationofpancreaticcancer
AT wohlfromms mir23a24inducedgenesilencingresultsinmesothelialcellintegrationofpancreaticcancer
AT meesst mir23a24inducedgenesilencingresultsinmesothelialcellintegrationofpancreaticcancer
AT haierj mir23a24inducedgenesilencingresultsinmesothelialcellintegrationofpancreaticcancer