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

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.

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

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.

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.

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.