Author(s): Abildgaard, Cecilie ; Do Canto, Luisa Matos ; Rainho, Cláudia Aparecida [UNESP] ; Marchi, Fabio Albuquerque ; Calanca, Naiade [UNESP] ; Waldstrøm, Marianne ; Steffensen, Karina Dahl ; Rogatto, Silvia Regina
Date: 2022
Persistent ID: http://hdl.handle.net/11449/234311
Origin: Oasisbr
Subject(s): chemotherapy; DNA methylation; drug resistance; lncRNA; ovarian cancer; transcrip-tomic analysis
Made available in DSpace on 2022-05-01T15:46:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Genetic 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.
Department of Clinical Genetics Lillebaelt University Hospital of Southern Denmark
Department of Oncology Lillebaelt University Hospital of Southern Denmark
Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
International Research Center CIPE—C. Camargo Cancer Center
Department of Pathology Lillebaelt University Hospital of Southern Denmark
Institute of Regional Health Research Faculty of Health Sciences University of Southern Denmark
Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
CAPES: 88887.310463/2018-00
