The Role of MNX1-AS1 in Ovarian Cancer Resistance and Tumor Progression via RNA-RNA Interactions.

Ovarian cancer (OC) remains one of the deadliest gynecological malignancies, largely due to late diagnosis and the emergence of resistance to platinum-based chemotherapy. Long non-coding RNAs (lncRNAs) have recently emerged as key regulators of tumor progression and therapeutic adaptation. In this study, we performed integrative transcriptomic profiling of patient-derived TCGA samples and carboplatin-resistant A2780 (CBDCA-R-A2780) cells to identify conserved lncRNAs associated with chemoresistance. Our analyses revealed extensive transcriptional remodeling across both datasets, with MNX1-AS1 consistently emerging as a central deregulated transcript. Differential expression analysis showed its robust upregulation in resistant cells and tumor tissues, accompanied by strong correlations with epithelial–mesenchymal transition (EMT)-related transcription factors such as FOXA1 and SNAI2, and inverse associations with epithelial markers including CDH1. Computational predictions using RIblast further identified specific MNX1-AS1 binding regions with hundreds of candidate miRNAs and mRNAs. Notably, genes such as SNAI2, FOXA1, and ZEB1 exhibited strong predicted hybridization energies and were upregulated in both resistant and tumor models, suggesting direct RNA-RNA interactions contributing to mesenchymal programming. Additional interactors included genes linked to stress response (IER2, FOSB) and invasion (MMP11, MMP1). Collectively, these findings highlight MNX1-AS1 as a potential regulator of transcriptional reprogramming in OC, positioning it as a promising prognostic biomarker and potential therapeutic target for overcoming chemoresistance.