Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer
Digital
- Autores:
-
Soto, Javier-Andres
Rodríguez‑Antolín, Carlos
Vera, Olga
Pernia, Olga
Esteban‑Rodriguez, Isabel
Diestro, Maria Dolores
Benitez, Javier
Sanchez‑Cabo, Fatima
Alvarez, Rafael
De Castro, Javier
Ibanez de Caceres, Inmaculada
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2021
- Institución:
- Universidad de Santander
- Repositorio:
- Repositorio Universidad de Santander
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.udes.edu.co:001/6153
- Acceso en línea:
- https://repositorio.udes.edu.co/handle/001/6153
- Palabra clave:
- PAX9
FKBP1B
Ovarian cancer
Methylation
Predictive
Platinum
Therapy
- Rights
- openAccess
- License
- © 2021. The Author(s).
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Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| title |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| spellingShingle |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer PAX9 FKBP1B Ovarian cancer Methylation Predictive Platinum Therapy |
| title_short |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| title_full |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| title_fullStr |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| title_full_unstemmed |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| title_sort |
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer |
| dc.creator.fl_str_mv |
Soto, Javier-Andres Rodríguez‑Antolín, Carlos Vera, Olga Pernia, Olga Esteban‑Rodriguez, Isabel Diestro, Maria Dolores Benitez, Javier Sanchez‑Cabo, Fatima Alvarez, Rafael De Castro, Javier Ibanez de Caceres, Inmaculada |
| dc.contributor.author.none.fl_str_mv |
Soto, Javier-Andres Rodríguez‑Antolín, Carlos Vera, Olga Pernia, Olga Esteban‑Rodriguez, Isabel Diestro, Maria Dolores Benitez, Javier Sanchez‑Cabo, Fatima Alvarez, Rafael De Castro, Javier Ibanez de Caceres, Inmaculada |
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Masira |
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PAX9 FKBP1B Ovarian cancer Methylation Predictive Platinum Therapy |
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PAX9 FKBP1B Ovarian cancer Methylation Predictive Platinum Therapy |
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Digital |
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2021 |
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2021-08-28 |
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2022-02-24T22:19:46Z |
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2022-02-24T22:19:46Z |
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eng |
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Soto JA, Rodríguez-Antolín C, Vera O, Pernía O, Esteban-Rodríguez I, Dolores Diestro M, Benitez J, Sánchez-Cabo F, Alvarez R, De Castro J, Ibanez de Cáceres I. Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer. Clin Epigenetics. 2021 Aug 28;13(1):167. doi: 10.1186/s13148-021-01149-8. PMID: 34454589; PMCID: PMC8401184. |
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Scopus |
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Clinical Epigenetics |
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© 2021. The Author(s). |
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Clinical Epigenetics |
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Reino Unido |
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Soto, Javier-Andres440906b9-866d-4bbd-945e-cf05c4ecec94-1Rodríguez‑Antolín, Carlos61610d1f-95ba-4a3e-92ec-7002ef02822d-1Vera, Olga3b2719a6-cc4b-47c6-8204-2b3e578ad426-1Pernia, Olga52db43df-c5d9-44e9-8317-f847318950a9-1Esteban‑Rodriguez, Isabel4ab2b190-aa6a-42fc-b6fd-de8815c870f2-1Diestro, Maria Dolores8a030935-a9dc-44c1-8726-ae192a7802c1-1Benitez, Javier5c2101d2-906a-464e-9039-64e0ce7eb920-1Sanchez‑Cabo, Fatima5bea6926-739f-43ce-968a-21e5e2593eac-1Alvarez, Rafael0c01cda2-1000-4a17-92eb-e24a864faa8f-1De Castro, Javier2bdc5905-00e4-4396-a775-9b5064da005e-1Ibanez de Caceres, Inmaculadab701f5ea-56f4-4726-b653-e0340f9b7b58-1Masira2022-02-24T22:19:46Z2022-02-24T22:19:46Z2021-08-28DigitalBackground: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies. Methods: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls. Results: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines. Conclusions: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient's progression and therapeutic response.Ciencias Médicas y de la Salud18 papplication/pdf10.1186/s13148-021-01149-8https://repositorio.udes.edu.co/handle/001/6153engClinical EpigeneticsReino Unido181113Soto JA, Rodríguez-Antolín C, Vera O, Pernía O, Esteban-Rodríguez I, Dolores Diestro M, Benitez J, Sánchez-Cabo F, Alvarez R, De Castro J, Ibanez de Cáceres I. Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer. Clin Epigenetics. 2021 Aug 28;13(1):167. doi: 10.1186/s13148-021-01149-8. PMID: 34454589; PMCID: PMC8401184.ScopusClinical Epigenetics© 2021. The Author(s).info:eu-repo/semantics/openAccessAtribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)https://creativecommons.org/licenses/by-nc/4.0/http://purl.org/coar/access_right/c_abf2https://clinicalepigeneticsjournal.biomedcentral.com/track/pdf/10.1186/s13148-021-01149-8.pdfPAX9FKBP1BOvarian cancerMethylationPredictivePlatinumTherapyTranscriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancerArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Todas las AudienciasPublicationORIGINALTranscriptional epigenetic regulation of Fkbp1-Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.pdfTranscriptional epigenetic regulation of Fkbp1-Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.pdfapplication/pdf234430https://repositorio.udes.edu.co/bitstreams/23aac291-b83d-4d93-9e89-64762c0f892d/download7c8ecbf1d7f6f855aa54faf9c4a5c925MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-859https://repositorio.udes.edu.co/bitstreams/299021e7-4040-465d-9d28-51d470a189e3/download38d94cf55aa1bf2dac1a736ac45c881cMD52TEXTTranscriptional epigenetic regulation of Fkbp1-Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.pdf.txtTranscriptional epigenetic regulation of Fkbp1-Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.pdf.txtExtracted texttext/plain5https://repositorio.udes.edu.co/bitstreams/20dbc4fb-5b71-41a7-826d-3e1f165b4758/download5dbe86c1111d64f45ba435df98fdc825MD53THUMBNAILTranscriptional epigenetic regulation of Fkbp1-Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.pdf.jpgTranscriptional epigenetic regulation of Fkbp1-Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.pdf.jpgGenerated Thumbnailimage/jpeg11613https://repositorio.udes.edu.co/bitstreams/b02ff938-cc43-415e-8959-4f1199705f43/download046b1acb4a2a7be0f985b6847fed4720MD54001/6153oai:repositorio.udes.edu.co:001/61532023-10-09 16:43:29.633https://creativecommons.org/licenses/by-nc/4.0/© 2021. 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