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Background <p>High-grade serous ovarian cancer (HGSOC) is the most aggressive ovarian cancer subtype, characterized by high recurrence, chemoresistance, and poor prognosis. Although competing endogenous RNA (ceRNA) networks involving long non-coding RNAs (lncRNAs) have been proposed as key regulators of tumor progression, their cell type–specific roles in HGSOC remain unclear.</p> Objectives <p>We aimed to identify lncRNA-associated ceRNA networks active within the HGSOC tumor microenvironment.</p> Methods <p>We performed an integrative analysis combining single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq datasets. Cancer cells were isolated, and coexpression analyses were conducted using high-dimensional weighted gene coexpression network analysis. The resulting ceRNA modules were validated and functionally annotated using The Cancer Genome Atlas and pathway enrichment analysis.</p> Results <p>Our analysis identified a cancer cell–specific ceRNA network involving <i>MIR100HG</i>, <i>mir-224-5p</i>, and <i>EYA4</i>. Interaction prediction and expression correlation analyses indicated that <i>MIR100HG</i> may function as a molecular sponge for <i>mir-224-5p</i>, thereby alleviating its suppression of <i>EYA4</i>. The presence of a 7mer-m8 seed match between <i>mir-224-5p</i> and <i>EYA4</i> supported this interaction. Pathway analysis suggested a link between the identified ceRNA network and the Wnt signaling pathway, a key driver of tumor initiation and metastasis.</p> Conclusion <p>The <i>MIR100HG–mir-224-5p–EYA4</i> ceRNA network may promote tumor progression by modulating Wnt signaling. These findings offer insights into a potential posttranscriptional regulatory mechanism in tumor development and therapeutic targeting in HGSOC.</p>

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Single-cell RNA sequencing reveals a putative lncRNA-associated ceRNA network in high-grade serous ovarian cancer

  • 期刊论文

  • 发表日期：

    2025年10月16日

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  • Johyeon Nam,
  • Mi-Ryung Han

摘要

Background

High-grade serous ovarian cancer (HGSOC) is the most aggressive ovarian cancer subtype, characterized by high recurrence, chemoresistance, and poor prognosis. Although competing endogenous RNA (ceRNA) networks involving long non-coding RNAs (lncRNAs) have been proposed as key regulators of tumor progression, their cell type–specific roles in HGSOC remain unclear.

Objectives

We aimed to identify lncRNA-associated ceRNA networks active within the HGSOC tumor microenvironment.

Methods

We performed an integrative analysis combining single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq datasets. Cancer cells were isolated, and coexpression analyses were conducted using high-dimensional weighted gene coexpression network analysis. The resulting ceRNA modules were validated and functionally annotated using The Cancer Genome Atlas and pathway enrichment analysis.

Results

Our analysis identified a cancer cell–specific ceRNA network involving MIR100HG, mir-224-5p, and EYA4. Interaction prediction and expression correlation analyses indicated that MIR100HG may function as a molecular sponge for mir-224-5p, thereby alleviating its suppression of EYA4. The presence of a 7mer-m8 seed match between mir-224-5p and EYA4 supported this interaction. Pathway analysis suggested a link between the identified ceRNA network and the Wnt signaling pathway, a key driver of tumor initiation and metastasis.

Conclusion

The MIR100HG–mir-224-5p–EYA4 ceRNA network may promote tumor progression by modulating Wnt signaling. These findings offer insights into a potential posttranscriptional regulatory mechanism in tumor development and therapeutic targeting in HGSOC.