The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms

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dc.contributor.authorAbildgaard, Cecilie
dc.contributor.authorDo Canto, Luisa Matos
dc.contributor.authorRainho, Cláudia Aparecida [UNESP]
dc.contributor.authorMarchi, Fabio Albuquerque
dc.contributor.authorCalanca, Naiade [UNESP]
dc.contributor.authorWaldstrøm, Marianne
dc.contributor.authorSteffensen, Karina Dahl
dc.contributor.authorRogatto, Silvia Regina
dc.contributor.institutionLillebaelt University Hospital of Southern Denmark
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionCIPE—C. Camargo Cancer Center
dc.contributor.institutionUniversity of Southern Denmark
dc.date.accessioned2022-05-01T15:46:19Z
dc.date.available2022-05-01T15:46:19Z
dc.date.issued2022-04-01
dc.description.abstractGenetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n = 111 OC samples) and internal datasets (n = 39 OC samples) to identify lncRNA candidates. A total of 4255 differentially expressed genes (DEGs) and 14529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.en
dc.description.affiliationDepartment of Clinical Genetics Lillebaelt University Hospital of Southern Denmark
dc.description.affiliationDepartment of Oncology Lillebaelt University Hospital of Southern Denmark
dc.description.affiliationDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationInternational Research Center CIPE—C. Camargo Cancer Center
dc.description.affiliationDepartment of Pathology Lillebaelt University Hospital of Southern Denmark
dc.description.affiliationInstitute of Regional Health Research Faculty of Health Sciences University of Southern Denmark
dc.description.affiliationUnespDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdCAPES: 88887.310463/2018-00
dc.identifierhttp://dx.doi.org/10.3390/cancers14071664
dc.identifier.citationCancers, v. 14, n. 7, 2022.
dc.identifier.doi10.3390/cancers14071664
dc.identifier.issn2072-6694
dc.identifier.scopus2-s2.0-85127021317
dc.identifier.urihttp://hdl.handle.net/11449/234311
dc.language.isoeng
dc.relation.ispartofCancers
dc.sourceScopus
dc.subjectchemotherapy
dc.subjectDNA methylation
dc.subjectdrug resistance
dc.subjectlncRNA
dc.subjectovarian cancer
dc.subjecttranscrip-tomic analysis
dc.titleThe Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanismsen
dc.typeArtigo

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