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LncRNA-driven alternative splicing landscapes associate with survival outcomes in ovarian cancer
Yan Cao1,2, Jian Zhao1, Shan He1
1Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.
Abstract:
Ovarian cancer (OV) has the highest mortality rate among gynecological malignancies, with limited improvement in survival despite emerging treatments, underscoring an urgent need for novel diagnostic and therapeutic targets. Alternative splicing (AS) plays critical roles in OV progression, and long non-coding RNAs (lncRNAs) have recently been implicated as splicing regulators in tumor development. However, the landscape of lncRNA-mediated splicing dysregulation in OV remains unexplored. Here, we performed a genome-wide analysis integrating 207 differentially expressed lncRNAs and 1201 abnormal AS events from OV transcriptomes, identifying 2545 co-expression pairs. By constructing multi-layer regulatory networks incorporating splicing factors, transcription factors, and microRNAs, and applying a restart random walk algorithm seeded with oncogenes, we prioritized 29 hub splicing-regulatory lncRNAs, of which 15 are significantly associated with OV survival. This study provides novel lncRNA biomarkers and mechanistic insights into splicing dysregulation in OV.
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