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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Micro-RNAs associated with the evolution of ovarian cancer cisplatin resistance
Bernadette M Boac1, Yin Xiong2, Douglas C Marchion2
1Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Objectives:
Ovarian cancer (OVCA) is the leading cause of mortality among women with gynecologic malignancy, in part due to the development of chemoresistance. We sought to identify micro-RNAs (miRNAs) associated with in vitro development of OVCA chemoresistance that may also represent potential targets for therapy.
Methods:
In this study, four OVCA cell lines (A2780CP, A2780S, IGROV1, and OVCAR5) were serially treated with cisplatin in parallel with measurements of miRNA expression changes.
Results:
Nine miRNAs were found to be associated with increasing cisplatin resistance (IC50) (p<0.01); however, only 5 of these miRNAs have publically available information. Pathway analysis identified 15 molecular signaling pathways that were represented by genes predicted to be targets of the 5 miRNAs (false discovery rate<0.05), 11 of which are associated with the epithelial-mesenchymal transition (EMT). Further analysis identified 2 of those pathways as being associated with overall survival in 218 patients with OVCA.
Conclusions:
Collectively, this panel of miRNAs associated with in vitro evolution of OVCA cisplatin resistance and the pathways identified to be associated with EMT and overall patient survival provide a framework for further investigations into EMT as a therapeutic target in patients with OVCA.
Insights
This study identifies micro-RNAs (miRNAs) linked to cisplatin resistance in ovarian cancer (OVCA) cells. These findings suggest the epithelial-mesenchymal transition (EMT) pathway may be a therapeutic target for improving patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer (OVCA) is a leading cause of cancer mortality in women.
- Chemoresistance significantly contributes to poor outcomes in OVCA patients.
- Identifying mechanisms of chemoresistance is crucial for developing effective therapies.
Purpose of the Study:
- To identify micro-RNAs (miRNAs) associated with cisplatin resistance in OVCA cell lines.
- To explore potential therapeutic targets for overcoming OVCA chemoresistance.
- To investigate the role of identified miRNAs and associated pathways in patient survival.
Main Methods:
- Serial cisplatin treatment of four OVCA cell lines (A2780CP, A2780S, IGROV1, OVCAR5).
- Measurement of micro-RNA (miRNA) expression changes during chemoresistance development.
- Bioinformatic pathway analysis of predicted miRNA targets.
Main Results:
- Nine miRNAs were significantly associated with increased cisplatin resistance (p<0.01).
- Pathway analysis revealed 15 molecular signaling pathways targeted by 5 miRNAs (FDR<0.05).
- Eleven of these pathways are linked to epithelial-mesenchymal transition (EMT); two pathways correlate with OVCA patient survival.
Conclusions:
- A panel of miRNAs is associated with cisplatin resistance evolution in OVCA.
- The epithelial-mesenchymal transition (EMT) pathway is implicated in OVCA chemoresistance and survival.
- EMT represents a potential therapeutic target for improving outcomes in ovarian cancer patients.
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