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.

Cancers
|March 25, 2022
PubMed

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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