DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer

Abstract High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resis...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Riikka J. Lund, Kaisa Huhtinen, Jussi Salmi, Juha Rantala, Elizabeth V. Nguyen, Robert Moulder, David R. Goodlett, Riitta Lahesmaa, Olli Carpén
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c01c760084d476eacca4d213f37d8c8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6c01c760084d476eacca4d213f37d8c8
record_format	dspace
spelling	oai:doaj.org-article:6c01c760084d476eacca4d213f37d8c82021-12-02T11:53:12ZDNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer10.1038/s41598-017-01624-42045-2322https://doaj.org/article/6c01c760084d476eacca4d213f37d8c82017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01624-4https://doaj.org/toc/2045-2322Abstract High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resistance, the DNA methylation and transcriptomic changes, associated with the development of drug resistance in high-grade serous ovarian cancer, were examined from patient derived malignant ascites cells. In parallel with large-scale transcriptome changes, cisplatin resistance was associated with loss of hypermethylation at several CpG sites primarily localized in the intergenic regions of the genome. The transcriptome and CpG methylome changes in response to cisplatin treatment of both sensitive and resistant cells were minimal, indicating the importance of post-translational mechanisms in regulating death or survival of the cells. The response of resistant cells to high concentrations of cisplatin revealed transcriptomic changes in potential key drivers of drug resistance, such as KLF4. Among the strongest changes was also induction of IL6 in resistant cells and the expression was further increased in response to cisplatin. Also, several other components of IL6 signaling were affected, further supporting previous observations on its importance in malignant transformation and development of drug resistance in ovarian cancer.Riikka J. LundKaisa HuhtinenJussi SalmiJuha RantalaElizabeth V. NguyenRobert MoulderDavid R. GoodlettRiitta LahesmaaOlli CarpénNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Riikka J. Lund Kaisa Huhtinen Jussi Salmi Juha Rantala Elizabeth V. Nguyen Robert Moulder David R. Goodlett Riitta Lahesmaa Olli Carpén DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
description	Abstract High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resistance, the DNA methylation and transcriptomic changes, associated with the development of drug resistance in high-grade serous ovarian cancer, were examined from patient derived malignant ascites cells. In parallel with large-scale transcriptome changes, cisplatin resistance was associated with loss of hypermethylation at several CpG sites primarily localized in the intergenic regions of the genome. The transcriptome and CpG methylome changes in response to cisplatin treatment of both sensitive and resistant cells were minimal, indicating the importance of post-translational mechanisms in regulating death or survival of the cells. The response of resistant cells to high concentrations of cisplatin revealed transcriptomic changes in potential key drivers of drug resistance, such as KLF4. Among the strongest changes was also induction of IL6 in resistant cells and the expression was further increased in response to cisplatin. Also, several other components of IL6 signaling were affected, further supporting previous observations on its importance in malignant transformation and development of drug resistance in ovarian cancer.
format	article
author	Riikka J. Lund Kaisa Huhtinen Jussi Salmi Juha Rantala Elizabeth V. Nguyen Robert Moulder David R. Goodlett Riitta Lahesmaa Olli Carpén
author_facet	Riikka J. Lund Kaisa Huhtinen Jussi Salmi Juha Rantala Elizabeth V. Nguyen Robert Moulder David R. Goodlett Riitta Lahesmaa Olli Carpén
author_sort	Riikka J. Lund
title	DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
title_short	DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
title_full	DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
title_fullStr	DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
title_full_unstemmed	DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
title_sort	dna methylation and transcriptome changes associated with cisplatin resistance in ovarian cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6c01c760084d476eacca4d213f37d8c8
work_keys_str_mv	AT riikkajlund dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT kaisahuhtinen dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT jussisalmi dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT juharantala dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT elizabethvnguyen dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT robertmoulder dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT davidrgoodlett dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT riittalahesmaa dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer AT ollicarpen dnamethylationandtranscriptomechangesassociatedwithcisplatinresistanceinovariancancer
_version_	1718394871876681728

DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer

Ejemplares similares