An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells
Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensit...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-03-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2018.1436364 |
| _version_ | 1797678962341576704 |
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| author | Olga Vera Carlos Rodriguez-Antolin Javier de Castro Florian A. Karreth Thomas A. Sellers Inmaculada Ibanez de Caceres |
| author_facet | Olga Vera Carlos Rodriguez-Antolin Javier de Castro Florian A. Karreth Thomas A. Sellers Inmaculada Ibanez de Caceres |
| author_sort | Olga Vera |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing. Selected candidate lncRNAs were further characterized by PCR, gene-ontology analysis, and targeted bisulfite sequencing. Differential expression in response to therapy was observed more frequently in cis-acting than in overlapping lncRNAs (78% vs. 22%, fold change ≥1.5), while significantly altered methylation profiles were more commonly associated with overlapping lncRNAs (29% vs. 8%; P value <0.001). Moreover, overlapping lncRNAs contain more CpG islands (CGIs) (25% vs. 17%) and the majority of CGI-containing overlapping lncRNAs share these CGIs with their associated coding genes (84%). The differences in expression between sensitive and resistant cell lines were replicated in 87% of the selected candidates (P<0.05), while our bioinformatics approach identifying differential methylation was confirmed in all of the selected lncRNAs (100%). Five lncRNAs under epigenetic regulation appear to be involved in cisplatin resistance (AC091814.2, AC141928.1, RP11-65J3.1-002, BX641110, and AF198444). These novel findings provide new insights into epigenetic mechanisms and acquired resistance to cisplatin that highlight specific lncRNAs, some with unknown function, that may signal strategies in epigenetic therapies. |
| first_indexed | 2024-03-11T23:06:34Z |
| format | Article |
| id | doaj.art-79286a7c152844f991a32afb7a09ab07 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:34Z |
| publishDate | 2018-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-79286a7c152844f991a32afb7a09ab072023-09-21T13:09:20ZengTaylor & Francis GroupEpigenetics1559-22941559-23082018-03-0113325126310.1080/15592294.2018.14363641436364An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cellsOlga Vera0Carlos Rodriguez-Antolin1Javier de Castro2Florian A. Karreth3Thomas A. Sellers4Inmaculada Ibanez de Caceres5La Paz University HospitalLa Paz University HospitalLa Paz University HospitalH. Lee Moffitt Cancer Center and Research InstituteH. Lee Moffitt Cancer Center and Research InstituteLa Paz University HospitalLong noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing. Selected candidate lncRNAs were further characterized by PCR, gene-ontology analysis, and targeted bisulfite sequencing. Differential expression in response to therapy was observed more frequently in cis-acting than in overlapping lncRNAs (78% vs. 22%, fold change ≥1.5), while significantly altered methylation profiles were more commonly associated with overlapping lncRNAs (29% vs. 8%; P value <0.001). Moreover, overlapping lncRNAs contain more CpG islands (CGIs) (25% vs. 17%) and the majority of CGI-containing overlapping lncRNAs share these CGIs with their associated coding genes (84%). The differences in expression between sensitive and resistant cell lines were replicated in 87% of the selected candidates (P<0.05), while our bioinformatics approach identifying differential methylation was confirmed in all of the selected lncRNAs (100%). Five lncRNAs under epigenetic regulation appear to be involved in cisplatin resistance (AC091814.2, AC141928.1, RP11-65J3.1-002, BX641110, and AF198444). These novel findings provide new insights into epigenetic mechanisms and acquired resistance to cisplatin that highlight specific lncRNAs, some with unknown function, that may signal strategies in epigenetic therapies.http://dx.doi.org/10.1080/15592294.2018.1436364lncrnadna methylationcisplatin-resistancelung/ovarian cancer |
| spellingShingle | Olga Vera Carlos Rodriguez-Antolin Javier de Castro Florian A. Karreth Thomas A. Sellers Inmaculada Ibanez de Caceres An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells Epigenetics lncrna dna methylation cisplatin-resistance lung/ovarian cancer |
| title | An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells |
| title_full | An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells |
| title_fullStr | An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells |
| title_full_unstemmed | An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells |
| title_short | An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells |
| title_sort | epigenomic approach to identifying differential overlapping and cis acting lncrnas in cisplatin resistant cancer cells |
| topic | lncrna dna methylation cisplatin-resistance lung/ovarian cancer |
| url | http://dx.doi.org/10.1080/15592294.2018.1436364 |
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