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  11. Epithelial Splicing Regulatory Protein 1 Promotes Peritoneal Dissemination Of Ovarian Cancer By Inducing The Formation Of Circular Rnas Modulating Epithelial Plasticity

Epithelial splicing regulatory protein 1 promotes peritoneal dissemination of ovarian cancer by inducing the formation of circular RNAs modulating epithelial plasticity

Guoqing Li1, Xiaoling Zhou2, Xiaoli Liu1

  • 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Cellular Signalling
|October 26, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Epithelial splicing regulatory protein 1 (ESRP1) drives ovarian cancer peritoneal metastasis by promoting cell plasticity. ESRP1 induces circular RNAs that stabilize key plasticity genes, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • Peritoneal metastases are common in ovarian cancer, worsening patient outcomes.
  • Tumor plasticity is crucial for cancer cell adaptation and spread during metastasis.
  • Epithelial splicing regulatory protein 1 (ESRP1) has been previously linked to ovarian cancer peritoneal metastasis and epithelial-mesenchymal plasticity.

Purpose of the Study:

  • To elucidate the mechanism by which ESRP1 influences epithelial plasticity and peritoneal metastasis in ovarian cancer.
  • To identify specific molecular players and pathways regulated by ESRP1 in this context.

Main Methods:

  • In vitro and in vivo experiments to assess ESRP1's role in ovarian cancer cell plasticity, growth, and dissemination.
  • High-throughput sequencing to identify ESRP1-regulated RNAs, including circular RNAs.
Keywords:
Circular RNAOvarian cancerPeritoneal metastasisTumor plasticity

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  • RNA-binding assays and molecular analyses to determine interactions between ESRP1, circular RNAs, target mRNAs, and associated proteins.

    • Main Results:

    • ESRP1 was confirmed to preserve epithelial plasticity in ovarian cancer cells.
    • ESRP1 enhances ovarian cancer cell growth and peritoneal dissemination.
    • ESRP1 induces the formation of circPAFAH1B2 and circUBAP2 by binding to intronic sequences.
    • These circular RNAs stabilize DKK3 and AHR mRNAs via IGF2BP2, critical for epithelial plasticity.

    Conclusions:

    • ESRP1 orchestrates a network involving circPAFAH1B2 and circUBAP2 to modulate epithelial plasticity and promote ovarian cancer peritoneal spread.
    • This ESRP1-driven network highlights ESRP1 and its induced circular RNAs as potential therapeutic targets for ovarian cancer treatment.