Object's details: Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors, Sonata Bis 2019/34/E/NZ7/00056, Sonata Bis-9 (dataset)

Provider:Repozytorium Uniwersytetu Łódzkiego

Description

Title:
Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors, Sonata Bis 2019/34/E/NZ7/00056, Sonata Bis-9 (dataset)
Creator:
Rogalska, Aneta
Contributor:
Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.;
aneta.rogalska@biol.uni.lodz.pl
Description:
Resistance to olaparib is the major obstacle in targeted therapy for ovarian cancer (OC) with poly(ADP-ribose) polymerase inhibitors (PARPis), prompting studies on novel combination therapies to enhance olaparib efficacy. Despite identifying various mechanisms, understanding how OC cells acquire PARPi resistance remains incomplete. This study investigated microRNA (miRNA) expression in olaparib-sensitive (PEO1, PEO4) and previously established olaparib-resistant OC cell lines (PEO1-OR) using high-throughput RT-qPCR and bioinformatic analyses. The role of miRNAs was explored regarding acquired resistance and resensitization with the ATR/CHK1 pathway inhibitors. Differentially expressed miRNAs were used to construct miRNA–mRNA regulatory networks and perform functional enrichment analyses for target genes with miRNet 2.0. TCGA-OV dataset was analyzed to explore the prognostic value of selected miRNAs and target genes in clinical samples. Potential processes associated with olaparib resistance, including cell proliferation, migration, cell cycle, and growth factor signaling were identified. Resensitized PEO1-OR cells were enriched in growth factor signaling via PDGF, EGFR, FGFR1, VEGFR2, and TGFβR, regulation of the cell cycle via the G2/M checkpoint, and caspase-mediated apoptosis. Antibody microarray analysis confirmed dysregulated growth factor expression. The addition of the ATR/CHK1 pathway inhibitors to olaparib downregulated FGF4, FGF6, NT-4, PLGF, and TGFβ1 exclusively in PEO1-OR cells. Survival and differential expression analyses for serous OC patients revealed prognostic miRNAs likely associated with olaparib resistance (miR-99b-5p, miR-424-3p, and miR-505-5p) and resensitization to olaparib (miR-324-5p and miR-424-3p). Essential miRNA–mRNA interactions were reconstructed based on prognostic miRNAs and target genes.;
This work was supported by the National Science Centre, Poland (Project grant number: Sonata Bis 2019/34/E/NZ7/00056).
Object availability:
free access
Rights:
Uznanie autorstwa 4.0 Międzynarodowe;
http://creativecommons.org/licenses/by/4.0
Date:
2024.07.02;
2024
Type:
Dataset
Language:
English
Format:
application/octet-stream
Subject:
ovarian cancer;
miRNA profiling;
olaparib;
resistance;
ATR/CHK1 pathway;
combination therapy;
growth factors;
bioinformatics;
TCGA data
Identifier: http://hdl.handle.net/11089/52737
Data provider:
Repozytorium Uniwersytetu Łódzkiego

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Object's details: Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors, Sonata Bis 2019/34/E/NZ7/00056, Sonata Bis-9 (dataset)

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