Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells
Cisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.688855/full |
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| author | Dilek Cansu Gurer İpek Erdogan Ulvi Ahmadov Merve Basol Merve Basol Osama Sweef Gulcin Cakan-Akdogan Bünyamin Akgül |
| author_facet | Dilek Cansu Gurer İpek Erdogan Ulvi Ahmadov Merve Basol Merve Basol Osama Sweef Gulcin Cakan-Akdogan Bünyamin Akgül |
| author_sort | Dilek Cansu Gurer |
| collection | DOAJ |
| description | Cisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs. |
| first_indexed | 2024-12-21T23:53:10Z |
| format | Article |
| id | doaj.art-3e1865b4f5e34f6b853f81b87783be3a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T23:53:10Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-3e1865b4f5e34f6b853f81b87783be3a2022-12-21T18:45:53ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.688855688855Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa CellsDilek Cansu Gurer0İpek Erdogan1Ulvi Ahmadov2Merve Basol3Merve Basol4Osama Sweef5Gulcin Cakan-Akdogan6Bünyamin Akgül7Noncoding RNA Laboratory, Department of Molecular Biology and Genetics, Ízmir, Institute of Technology, Izmir, TurkeyNoncoding RNA Laboratory, Department of Molecular Biology and Genetics, Ízmir, Institute of Technology, Izmir, TurkeyNoncoding RNA Laboratory, Department of Molecular Biology and Genetics, Ízmir, Institute of Technology, Izmir, TurkeyIzmir Biomedicine and Genome Center, Ízmir, TurkeyIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Ízmir, TurkeyNoncoding RNA Laboratory, Department of Molecular Biology and Genetics, Ízmir, Institute of Technology, Izmir, TurkeyIzmir Biomedicine and Genome Center, Ízmir, TurkeyNoncoding RNA Laboratory, Department of Molecular Biology and Genetics, Ízmir, Institute of Technology, Izmir, TurkeyCisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs.https://www.frontiersin.org/articles/10.3389/fcell.2021.688855/fullcisplatinapoptosislncRNAsproliferationmetastasistranscriptomics |
| spellingShingle | Dilek Cansu Gurer İpek Erdogan Ulvi Ahmadov Merve Basol Merve Basol Osama Sweef Gulcin Cakan-Akdogan Bünyamin Akgül Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells Frontiers in Cell and Developmental Biology cisplatin apoptosis lncRNAs proliferation metastasis transcriptomics |
| title | Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells |
| title_full | Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells |
| title_fullStr | Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells |
| title_full_unstemmed | Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells |
| title_short | Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells |
| title_sort | transcriptomics profiling identifies cisplatin inducible death receptor 5 antisense long non coding rna as a modulator of proliferation and metastasis in hela cells |
| topic | cisplatin apoptosis lncRNAs proliferation metastasis transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.688855/full |
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