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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Long Non-Coding RNA-Based Functional Prediction Reveals Novel Targets in Notch-Upregulated Ovarian Cancer
Seonhyang Jeong1, Sunmi Park1, Young Suk Jo1
1Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Abstract:
Notch signaling is a druggable target in high-grade serous ovarian cancers; however, its complexity is not clearly understood. Recent revelations of the biological roles of lncRNAs have led to an increased interest in the oncogenic action of lncRNAs in various cancers. In this study, we performed in silico analyses using The Cancer Genome Atlas data to discover novel Notch-related lncRNAs and validated our transcriptome data via NOTCH1/3 silencing in serous ovarian cancer cells. The expression of novel Notch-related lncRNAs was down-regulated by a Notch inhibitor and was upregulated in high-grade serous ovarian cancers, compared to benign or borderline ovarian tumors. Functionally, Notch-related lncRNAs were tightly linked to Notch-related changes in diverse gene expressions. Notably, genes related to DNA repair and spermatogenesis showed specific correlations with Notch-related lncRNAs. Master transcription factors, including EGR1, CTCF, GABPα, and E2F4 might orchestrate the upregulation of Notch-related lncRNAs, along with the associated genes. The discovery of Notch-related lncRNAs significantly contributes to our understanding of the complex crosstalk of Notch signaling with other oncogenic pathways at the transcriptional level.
Insights
This study identifies novel long non-coding RNAs (lncRNAs) linked to Notch signaling in ovarian cancer. These Notch-related lncRNAs are upregulated in high-grade serous ovarian cancers and correlate with DNA repair and spermatogenesis genes.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Notch signaling is a critical target in high-grade serous ovarian cancer, but its complexity remains incompletely understood.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in oncogenesis, prompting investigation into their involvement with Notch signaling.
Purpose of the Study:
- To discover novel Notch-related lncRNAs in ovarian cancer using in silico analyses.
- To validate the role of these lncRNAs in serous ovarian cancer cells through gene silencing experiments.
Main Methods:
- In silico analysis of The Cancer Genome Atlas (TCGA) data to identify Notch-related lncRNAs.
- Transcriptome data validation via NOTCH1/3 silencing in serous ovarian cancer cell lines.
- Correlation analysis between lncRNA expression and gene expression profiles.
Main Results:
- Identified novel Notch-related lncRNAs that are downregulated by Notch inhibitors.
- Observed upregulation of these lncRNAs in high-grade serous ovarian cancers compared to benign or borderline tumors.
- Found significant correlations between Notch-related lncRNAs and genes involved in DNA repair and spermatogenesis.
- Identified potential master transcription factors (EGR1, CTCF, GABPα, E2F4) regulating these lncRNAs.
Conclusions:
- The discovery of Notch-related lncRNAs enhances the understanding of Notch signaling crosstalk with oncogenic pathways at the transcriptional level.
- These lncRNAs represent potential biomarkers or therapeutic targets in high-grade serous ovarian cancer.
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