Alternative splicing in ovarian cancer.

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• Ovarian cancer is a leading cause of gynecologic cancer death, with poor survival rates due to late detection and treatment resistance.
• Alternative splicing, a key regulator of gene expression, plays a critical role in cancer development and progression.
• Understanding the molecular signatures of ovarian cancer is crucial for identifying novel therapeutic targets and improving patient outcomes.

Purpose of the Study:

• To review the multifaceted roles of alternative splicing in ovarian cancer biology, including its impact on proliferation, metastasis, and chemoresistance.
• To highlight altered splicing machinery and specific splicing variants involved in ovarian cancer tumorigenesis and drug resistance.
• To discuss the potential of alternative splicing as a diagnostic marker and therapeutic target for ovarian cancer.

Main Methods:

• Review of existing literature on alternative splicing in ovarian cancer.
• Analysis of The Cancer Genome Atlas (TCGA) RNA-seq data and clinical information to develop prognostic models.
• Summary of experimental evidence on targeting splicing factors and events in ovarian cancer models.

Main Results:

• Increased expression of spliceosome components and splicing factors (e.g., BUD31, SF3B4) is linked to ovarian cancer.
• Specific splicing variants (e.g., CD44, ECM1, KAI1) influence tumorigenesis and drug resistance.
• Novel splicing events (PIGV|1299|AP, FLT3LG|50,941|AP) are identified in prognostic models, correlating with patient outcomes.
• Targeting splicing factor BUD31 or inducing BCL2L12 exon skipping promotes apoptosis in ovarian cancer cells.
• Bevacizumab targeting VEGF-A isoforms shows efficacy in advanced ovarian cancer.

Conclusions:

• Alternative splicing is a pivotal determinant in ovarian cancer biology, influencing prognosis, immune microenvironment, and drug sensitivity.
• Novel splicing variants represent promising targets for further functional characterization and therapeutic development.
• Targeting alternative splicing pathways offers a promising strategy for novel diagnostics and therapeutics in ovarian cancer.