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Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors

Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix...

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Autores principales: O’Neill, Fiona, Allen-Coyle, Taylor-Jade, Roche, Sandra, Meiller, Justine, Conlon, Neil T., Swan, Niall, Straubinger, Robert M., Geoghegan, Justin, Straubinger, Ninfa L., Conlon, Kevin, McDermott, Ray, O’Sullivan, Finbarr, Henry, Michael, Meleady, Paula, McVey, Gerard, O’Connor, Robert, Moriarty, Michael, Clynes, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057657/
https://www.ncbi.nlm.nih.gov/pubmed/36983764
http://dx.doi.org/10.3390/life13030608
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author O’Neill, Fiona
Allen-Coyle, Taylor-Jade
Roche, Sandra
Meiller, Justine
Conlon, Neil T.
Swan, Niall
Straubinger, Robert M.
Geoghegan, Justin
Straubinger, Ninfa L.
Conlon, Kevin
McDermott, Ray
O’Sullivan, Finbarr
Henry, Michael
Meleady, Paula
McVey, Gerard
O’Connor, Robert
Moriarty, Michael
Clynes, Martin
author_facet O’Neill, Fiona
Allen-Coyle, Taylor-Jade
Roche, Sandra
Meiller, Justine
Conlon, Neil T.
Swan, Niall
Straubinger, Robert M.
Geoghegan, Justin
Straubinger, Ninfa L.
Conlon, Kevin
McDermott, Ray
O’Sullivan, Finbarr
Henry, Michael
Meleady, Paula
McVey, Gerard
O’Connor, Robert
Moriarty, Michael
Clynes, Martin
author_sort O’Neill, Fiona
collection PubMed
description Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix GeneChip miRNA 4.0 array. A transcriptome analysis console (TAC) was used to generate comparative lists of up- and downregulated miRNAs for the comparisons, tumor vs. normal and F1 PDX vs. tumor. Particular attention was paid to miRNAs that were changed in the same direction in both comparisons. We identified the involvement in pancreatic tumor tissue of several miRNAs, including miR4534, miR3154, and miR4742, not previously highlighted as being involved in this type of cancer. Investigation in the parallel mRNA and protein lists from the same samples allowed the elimination of proteins where altered expression correlated with corresponding mRNA levels and was thus less likely to be miRNA regulated. Using the remaining differential expression protein lists for proteins predicted to be targeted for differentially expressed miRNA on our list, we were able to tentatively ascribe specific protein changes to individual miRNA. Particularly interesting target proteins for miRs 615-3p, 2467-3p, 4742-5p, 509-5p, and 605-3p were identified. Prominent among the protein targets are enzymes involved in aldehyde metabolism and membrane transport and trafficking. These results may help to uncover vulnerabilities that could enable novel approaches to treating pancreatic cancer.
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spelling pubmed-100576572023-03-30 Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors O’Neill, Fiona Allen-Coyle, Taylor-Jade Roche, Sandra Meiller, Justine Conlon, Neil T. Swan, Niall Straubinger, Robert M. Geoghegan, Justin Straubinger, Ninfa L. Conlon, Kevin McDermott, Ray O’Sullivan, Finbarr Henry, Michael Meleady, Paula McVey, Gerard O’Connor, Robert Moriarty, Michael Clynes, Martin Life (Basel) Article Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix GeneChip miRNA 4.0 array. A transcriptome analysis console (TAC) was used to generate comparative lists of up- and downregulated miRNAs for the comparisons, tumor vs. normal and F1 PDX vs. tumor. Particular attention was paid to miRNAs that were changed in the same direction in both comparisons. We identified the involvement in pancreatic tumor tissue of several miRNAs, including miR4534, miR3154, and miR4742, not previously highlighted as being involved in this type of cancer. Investigation in the parallel mRNA and protein lists from the same samples allowed the elimination of proteins where altered expression correlated with corresponding mRNA levels and was thus less likely to be miRNA regulated. Using the remaining differential expression protein lists for proteins predicted to be targeted for differentially expressed miRNA on our list, we were able to tentatively ascribe specific protein changes to individual miRNA. Particularly interesting target proteins for miRs 615-3p, 2467-3p, 4742-5p, 509-5p, and 605-3p were identified. Prominent among the protein targets are enzymes involved in aldehyde metabolism and membrane transport and trafficking. These results may help to uncover vulnerabilities that could enable novel approaches to treating pancreatic cancer. MDPI 2023-02-22 /pmc/articles/PMC10057657/ /pubmed/36983764 http://dx.doi.org/10.3390/life13030608 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
O’Neill, Fiona
Allen-Coyle, Taylor-Jade
Roche, Sandra
Meiller, Justine
Conlon, Neil T.
Swan, Niall
Straubinger, Robert M.
Geoghegan, Justin
Straubinger, Ninfa L.
Conlon, Kevin
McDermott, Ray
O’Sullivan, Finbarr
Henry, Michael
Meleady, Paula
McVey, Gerard
O’Connor, Robert
Moriarty, Michael
Clynes, Martin
Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors
title Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors
title_full Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors
title_fullStr Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors
title_full_unstemmed Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors
title_short Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors
title_sort alteration in levels of specific mirnas and their potential protein targets between human pancreatic cancer samples, adjacent normal tissue, and xenografts derived from these tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057657/
https://www.ncbi.nlm.nih.gov/pubmed/36983764
http://dx.doi.org/10.3390/life13030608
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