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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
Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer
Jing Zou1, Fuqiang Yin2, Qi Wang1
1Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi, P.R. China.
Abstract:
The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset GSE33482, GSE28646, and GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), and then their associations with drug resistance was analyzed by comprehensive bioinformatic analyses. Nine microRNAs (microRNA-199a-5p, microRNA-199a-3p, microRNA-199b-3p, microRNA-215, microRNA-335, microRNA-18b, microRNA-363, microRNA-645 and microRNA-141) and 38 genes were identified to be differentially expressed in drug-resistant ovarian cancer cells, with seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA and PI15) exhibited exactly the same expression trends in all three microarrays. Biological process annotation and pathway enrichment analysis of the 9 microRNAs and 38 genes identified several drug resistant-related signaling pathways, and the microRNA-mRNA interaction revealed the existence of a targeted regulatory relationship between the 9 microRNAs and most of the 38 genes. The expression of 9 microRNAs and the 7 genes by qRT-PCR in SKOV3/DDP and A2780/DDP cells indicating a consistent expression profile with the microarrays. Among those, the expression of EPHA7 and PI15 were negatively correlated with that of microRNA-141, and they were also identified as potential targets of this microRNA via microRNA-mRNA interaction. We thus concluded that microRNA-141, EPHA7, and PI15 might jointly participate in the regulation of drug resistance in ovarian cancer and serve as potential targets in targeted therapies.
Insights
This study identified nine microRNAs and 38 genes linked to ovarian cancer drug resistance. MicroRNA-141, EPHA7, and PI15 were found to potentially work together in regulating drug resistance, offering new therapeutic targets.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Ovarian cancer drug resistance poses a significant clinical challenge.
- Identifying molecular mechanisms underlying drug resistance is crucial for developing effective treatments.
Purpose of the Study:
- To identify microRNAs and genes associated with drug resistance in ovarian cancer using microarray data.
- To investigate the regulatory relationships between identified microRNAs and genes.
- To explore potential therapeutic targets for overcoming drug resistance.
Main Methods:
- Downloaded and analyzed microarray datasets (GS54665, GSE33482, GSE28646, GSE15372) from the Gene Expression Omnibus database.
- Screened dysregulated microRNAs and genes using GEO2R and validated findings with real-time quantitative PCR (qRT-PCR) in ovarian cancer cell lines (SKOV3/DDP, A2780/DDP).
- Performed comprehensive bioinformatic analyses, including pathway enrichment and microRNA-mRNA interaction analysis.
Main Results:
- Identified nine differentially expressed microRNAs and 38 genes in drug-resistant ovarian cancer cells.
- Seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA, PI15) showed consistent expression trends across multiple datasets.
- Found a negative correlation between microRNA-141 and EPHA7/PI15, suggesting a targeted regulatory relationship.
Conclusions:
- MicroRNA-141, EPHA7, and PI15 may jointly regulate drug resistance in ovarian cancer.
- These molecules represent potential targets for novel therapeutic strategies against drug-resistant ovarian cancer.
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