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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/13/3/608 |
| _version_ | 1797610668737691648 |
|---|---|
| author | Fiona O’Neill Taylor-Jade Allen-Coyle Sandra Roche Justine Meiller Neil T. Conlon Niall Swan Robert M. Straubinger Justin Geoghegan Ninfa L. Straubinger Kevin Conlon Ray McDermott Finbarr O’Sullivan Michael Henry Paula Meleady Gerard McVey Robert O’Connor Michael Moriarty Martin Clynes |
| author_facet | Fiona O’Neill Taylor-Jade Allen-Coyle Sandra Roche Justine Meiller Neil T. Conlon Niall Swan Robert M. Straubinger Justin Geoghegan Ninfa L. Straubinger Kevin Conlon Ray McDermott Finbarr O’Sullivan Michael Henry Paula Meleady Gerard McVey Robert O’Connor Michael Moriarty Martin Clynes |
| author_sort | Fiona O’Neill |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T06:17:29Z |
| format | Article |
| id | doaj.art-a7c66f94d63d447e9e0fc09d6ba50f6e |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T06:17:29Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-a7c66f94d63d447e9e0fc09d6ba50f6e2023-11-17T12:09:53ZengMDPI AGLife2075-17292023-02-0113360810.3390/life13030608Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These TumorsFiona O’Neill0Taylor-Jade Allen-Coyle1Sandra Roche2Justine Meiller3Neil T. Conlon4Niall Swan5Robert M. Straubinger6Justin Geoghegan7Ninfa L. Straubinger8Kevin Conlon9Ray McDermott10Finbarr O’Sullivan11Michael Henry12Paula Meleady13Gerard McVey14Robert O’Connor15Michael Moriarty16Martin Clynes17National Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandSt. Vincent’s University Hospital, D04 T6F4 Dublin, IrelandDepartment of Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY 14214, USASt. Vincent’s University Hospital, D04 T6F4 Dublin, IrelandDepartment of Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY 14214, USASt. Vincent’s University Hospital, D04 T6F4 Dublin, IrelandSt. Vincent’s University Hospital, D04 T6F4 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandSt. Luke’s Hospital, Rathgar, D06 HH36 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandNational Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, IrelandHerein, 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.https://www.mdpi.com/2075-1729/13/3/608pancreatic cancermiRNAPDXtumour |
| spellingShingle | Fiona O’Neill Taylor-Jade Allen-Coyle Sandra Roche Justine Meiller Neil T. Conlon Niall Swan Robert M. Straubinger Justin Geoghegan Ninfa L. Straubinger Kevin Conlon Ray McDermott Finbarr O’Sullivan Michael Henry Paula Meleady Gerard McVey Robert O’Connor Michael Moriarty Martin Clynes 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 Life pancreatic cancer miRNA PDX tumour |
| 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 | pancreatic cancer miRNA PDX tumour |
| url | https://www.mdpi.com/2075-1729/13/3/608 |
| work_keys_str_mv | AT fionaoneill alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT taylorjadeallencoyle alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT sandraroche alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT justinemeiller alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT neiltconlon alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT niallswan alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT robertmstraubinger alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT justingeoghegan alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT ninfalstraubinger alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT kevinconlon alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT raymcdermott alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT finbarrosullivan alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT michaelhenry alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT paulameleady alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT gerardmcvey alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT robertoconnor alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT michaelmoriarty alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors AT martinclynes alterationinlevelsofspecificmirnasandtheirpotentialproteintargetsbetweenhumanpancreaticcancersamplesadjacentnormaltissueandxenograftsderivedfromthesetumors |