Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line
Cisplatin is a chemotherapy drug that kills cancer cells by damaging their DNA. In human cells, this damage is repaired primarily by nucleotide excision repair. While cisplatin is generally effective, many cancers exhibit initial or acquired resistance to it. Here, we studied cisplatin resistance in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5814 |
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| author | Hadar Golan Berman Pooja Chauhan Shira Shalev Hiba Hassanain Avital Parnas Sheera Adar |
| author_facet | Hadar Golan Berman Pooja Chauhan Shira Shalev Hiba Hassanain Avital Parnas Sheera Adar |
| author_sort | Hadar Golan Berman |
| collection | DOAJ |
| description | Cisplatin is a chemotherapy drug that kills cancer cells by damaging their DNA. In human cells, this damage is repaired primarily by nucleotide excision repair. While cisplatin is generally effective, many cancers exhibit initial or acquired resistance to it. Here, we studied cisplatin resistance in a defined cell line system. We conducted a comprehensive genomic characterization of the cisplatin-sensitive A2780 ovarian cancer cell line compared to A2780cis, its resistant derivative. The resistant cells acquired less damage, but had similar repair kinetics. Genome-wide mapping of nucleotide excision repair showed a shift in the resistant cells from global genome towards transcription-coupled repair. By mapping gene expression changes following cisplatin treatment, we identified 56 upregulated genes that have higher basal expression in the resistant cell line, suggesting they are primed for a cisplatin response. More than half of these genes are novel to cisplatin- or damage-response. Six out of seven primed genes tested were upregulated in response to cisplatin in additional cell lines, making them attractive candidates for future investigation. These novel candidates for cisplatin resistance could prove to be important prognostic markers or targets for tailored combined therapy in the future. |
| first_indexed | 2024-03-10T10:54:22Z |
| format | Article |
| id | doaj.art-251e9452f69646cf9ebd1dda3b939d7a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:54:22Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-251e9452f69646cf9ebd1dda3b939d7a2023-11-21T21:55:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211581410.3390/ijms22115814Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell LineHadar Golan Berman0Pooja Chauhan1Shira Shalev2Hiba Hassanain3Avital Parnas4Sheera Adar5Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem 91120, IsraelCisplatin is a chemotherapy drug that kills cancer cells by damaging their DNA. In human cells, this damage is repaired primarily by nucleotide excision repair. While cisplatin is generally effective, many cancers exhibit initial or acquired resistance to it. Here, we studied cisplatin resistance in a defined cell line system. We conducted a comprehensive genomic characterization of the cisplatin-sensitive A2780 ovarian cancer cell line compared to A2780cis, its resistant derivative. The resistant cells acquired less damage, but had similar repair kinetics. Genome-wide mapping of nucleotide excision repair showed a shift in the resistant cells from global genome towards transcription-coupled repair. By mapping gene expression changes following cisplatin treatment, we identified 56 upregulated genes that have higher basal expression in the resistant cell line, suggesting they are primed for a cisplatin response. More than half of these genes are novel to cisplatin- or damage-response. Six out of seven primed genes tested were upregulated in response to cisplatin in additional cell lines, making them attractive candidates for future investigation. These novel candidates for cisplatin resistance could prove to be important prognostic markers or targets for tailored combined therapy in the future.https://www.mdpi.com/1422-0067/22/11/5814cisplatincancerresistanceDNA damageDNA repairnucleotide excision repair |
| spellingShingle | Hadar Golan Berman Pooja Chauhan Shira Shalev Hiba Hassanain Avital Parnas Sheera Adar Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line International Journal of Molecular Sciences cisplatin cancer resistance DNA damage DNA repair nucleotide excision repair |
| title | Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line |
| title_full | Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line |
| title_fullStr | Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line |
| title_full_unstemmed | Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line |
| title_short | Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line |
| title_sort | genomic characterization of cisplatin response uncovers priming of cisplatin induced genes in a resistant cell line |
| topic | cisplatin cancer resistance DNA damage DNA repair nucleotide excision repair |
| url | https://www.mdpi.com/1422-0067/22/11/5814 |
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