RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines
Phenanthriplatin is a new monofunctional platinum(II) complex that binds only one strand of DNA and acts by blocking gene transcription, but its effect on gene regulation has not been characterized relative to the traditional platinum-based complex, cisplatin. A549 non-small cell lung cancer and IMR...
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MDPI AG
2020-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/12/2637 |
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| author | Jerry D. Monroe Satya A. Moolani Elvin N. Irihamye Joshua S. Speed Yann Gibert Michael E. Smith |
| author_facet | Jerry D. Monroe Satya A. Moolani Elvin N. Irihamye Joshua S. Speed Yann Gibert Michael E. Smith |
| author_sort | Jerry D. Monroe |
| collection | DOAJ |
| description | Phenanthriplatin is a new monofunctional platinum(II) complex that binds only one strand of DNA and acts by blocking gene transcription, but its effect on gene regulation has not been characterized relative to the traditional platinum-based complex, cisplatin. A549 non-small cell lung cancer and IMR90 lung fibroblast cells were treated with cisplatin, phenanthriplatin, or a control and then their RNA transcripts were subjected to next generation sequencing analysis. DESeq2 and CuffDiff2 were used to identify up- and downregulated genes and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to identify pathways and functions. We found that phenanthriplatin may regulate the genes GPRC5a, TFF1, and TNFRSF10D, which act through p53 to control apoptosis, differently or to a greater extent than cisplatin, and that it, unlike cisplatin, could upregulate ATP5MD, a gene which signals through the Wnt/β catenin pathway. Furthermore, phenanthriplatin caused unique or enhanced effects compared to cisplatin on genes regulating the cytoskeleton, cell migration, and proliferation, e.g., AGAP1, DIAPH2, GDF15, and THSD1 (<i>p</i> < 0.05; <i>q</i> < 0.05). Phenanthriplatin may modulate some oncogenes differently than cisplatin potentially leading to improved clinical outcome, but this monofunctional complex should be carefully matched with cancer gene data to be successfully applied in chemotherapy. |
| first_indexed | 2024-03-10T14:14:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:14:58Z |
| publishDate | 2020-12-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-c86c9c67c3ee4651aea797a72875d20f2023-11-20T23:53:45ZengMDPI AGCells2073-44092020-12-01912263710.3390/cells9122637RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell LinesJerry D. Monroe0Satya A. Moolani1Elvin N. Irihamye2Joshua S. Speed3Yann Gibert4Michael E. Smith5Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Biology, Western Kentucky University, Bowling Green, KY 42101-1080, USADepartment of Biology, Western Kentucky University, Bowling Green, KY 42101-1080, USADepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Biology, Western Kentucky University, Bowling Green, KY 42101-1080, USAPhenanthriplatin is a new monofunctional platinum(II) complex that binds only one strand of DNA and acts by blocking gene transcription, but its effect on gene regulation has not been characterized relative to the traditional platinum-based complex, cisplatin. A549 non-small cell lung cancer and IMR90 lung fibroblast cells were treated with cisplatin, phenanthriplatin, or a control and then their RNA transcripts were subjected to next generation sequencing analysis. DESeq2 and CuffDiff2 were used to identify up- and downregulated genes and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to identify pathways and functions. We found that phenanthriplatin may regulate the genes GPRC5a, TFF1, and TNFRSF10D, which act through p53 to control apoptosis, differently or to a greater extent than cisplatin, and that it, unlike cisplatin, could upregulate ATP5MD, a gene which signals through the Wnt/β catenin pathway. Furthermore, phenanthriplatin caused unique or enhanced effects compared to cisplatin on genes regulating the cytoskeleton, cell migration, and proliferation, e.g., AGAP1, DIAPH2, GDF15, and THSD1 (<i>p</i> < 0.05; <i>q</i> < 0.05). Phenanthriplatin may modulate some oncogenes differently than cisplatin potentially leading to improved clinical outcome, but this monofunctional complex should be carefully matched with cancer gene data to be successfully applied in chemotherapy.https://www.mdpi.com/2073-4409/9/12/2637next generation sequencingcancermonofunctional platinum(II) complexpathway analysiscisplatin |
| spellingShingle | Jerry D. Monroe Satya A. Moolani Elvin N. Irihamye Joshua S. Speed Yann Gibert Michael E. Smith RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines Cells next generation sequencing cancer monofunctional platinum(II) complex pathway analysis cisplatin |
| title | RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines |
| title_full | RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines |
| title_fullStr | RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines |
| title_full_unstemmed | RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines |
| title_short | RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines |
| title_sort | rna seq analysis of cisplatin and the monofunctional platinum ii complex phenanthriplatin in a549 non small cell lung cancer and imr90 lung fibroblast cell lines |
| topic | next generation sequencing cancer monofunctional platinum(II) complex pathway analysis cisplatin |
| url | https://www.mdpi.com/2073-4409/9/12/2637 |
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