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 ovarian tumor samples and carboplatin-resistant A2780 (CBDCA-R-A2780) cells to identify lncRNAs whose dysregulation overlaps between a cell-line resistance model and patient tumors. Our analyses revealed extensive transcriptional remodeling across both datasets, with <i>MNX1</i>-<i>AS1</i> consistently emerging as a strongly deregulated transcript. Differential expression analysis showed robust upregulation of <i>MNX1</i>-<i>AS1</i> in resistant cells and tumor tissues, accompanied by correlations with epithelial-mesenchymal transition (EMT)-related transcription factors such as <i>FOXA1</i> and <i>SNAI2</i> and inverse associations with epithelial markers including <i>CDH1</i>. Computational predictions using RIblast identified specific <i>MNX1</i>-<i>AS1</i> binding regions with candidate miRNAs and mRNAs, prioritizing EMT-related transcripts (e.g., <i>SNAI2</i>, <i>FOXA1</i>, <i>ZEB1</i>) with favorable hybridization energies for future validation. Additional prioritized interactors included genes linked to stress response (<i>IER2</i>, <i>FOSB</i>) and invasion (<i>MMP11</i>, <i>MMP1</i>). Because A2780 has been discussed as an endometrioid-like/non-serous ovarian cancer model, mechanistic inferences primarily apply to this in vitro context, while TCGA analyses provide associative support rather than mechanistic validation. Collectively, these findings highlight <i>MNX1</i>-<i>AS1</i> as a candidate regulator associated with transcriptional reprogramming in OC and a promising prognostic biomarker warranting further functional testing.