Alternative splicing in ovarian cancer
Abstract Ovarian cancer is the second leading cause of gynecologic cancer death worldwide, with only 20% of cases detected early due to its elusive nature, limiting successful treatment. Most deaths occur from the disease progressing to advanced stages. Despite advances in chemo- and immunotherapy,...
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| Format: | Article |
| Language: | English |
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BMC
2024-10-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01880-8 |
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| author | Liwei Wei Yisheng Li Jiawang Chen Yuanmei Wang Jianmin Wu Huanming Yang Yi Zhang |
| author_facet | Liwei Wei Yisheng Li Jiawang Chen Yuanmei Wang Jianmin Wu Huanming Yang Yi Zhang |
| author_sort | Liwei Wei |
| collection | DOAJ |
| description | Abstract Ovarian cancer is the second leading cause of gynecologic cancer death worldwide, with only 20% of cases detected early due to its elusive nature, limiting successful treatment. Most deaths occur from the disease progressing to advanced stages. Despite advances in chemo- and immunotherapy, the 5-year survival remains below 50% due to high recurrence and chemoresistance. Therefore, leveraging new research perspectives to understand molecular signatures and identify novel therapeutic targets is crucial for improving the clinical outcomes of ovarian cancer. Alternative splicing, a fundamental mechanism of post-transcriptional gene regulation, significantly contributes to heightened genomic complexity and protein diversity. Increased awareness has emerged about the multifaceted roles of alternative splicing in ovarian cancer, including cell proliferation, metastasis, apoptosis, immune evasion, and chemoresistance. We begin with an overview of altered splicing machinery, highlighting increased expression of spliceosome components and associated splicing factors like BUD31, SF3B4, and CTNNBL1, and their relationships to ovarian cancer. Next, we summarize the impact of specific variants of CD44, ECM1, and KAI1 on tumorigenesis and drug resistance through diverse mechanisms. Recent genomic and bioinformatics advances have enhanced our understanding. By incorporating data from The Cancer Genome Atlas RNA-seq, along with clinical information, a series of prognostic models have been developed, which provided deeper insights into how the splicing influences prognosis, overall survival, the immune microenvironment, and drug sensitivity and resistance in ovarian cancer patients. Notably, novel splicing events, such as PIGV|1299|AP and FLT3LG|50,941|AP, have been identified in multiple prognostic models and are associated with poorer and improved prognosis, respectively. These novel splicing variants warrant further functional characterization to unlock the underlying molecular mechanisms. Additionally, experimental evidence has underscored the potential therapeutic utility of targeting alternative splicing events, exemplified by the observation that knockdown of splicing factor BUD31 or antisense oligonucleotide-induced BCL2L12 exon skipping promotes apoptosis of ovarian cancer cells. In clinical settings, bevacizumab, a humanized monoclonal antibody that specifically targets the VEGF-A isoform, has demonstrated beneficial effects in the treatment of patients with advanced epithelial ovarian cancer. In conclusion, this review constitutes the first comprehensive and detailed exposition of the intricate interplay between alternative splicing and ovarian cancer, underscoring the significance of alternative splicing events as pivotal determinants in cancer biology and as promising avenues for future diagnostic and therapeutic intervention. |
| format | Article |
| id | doaj-art-9daab3cd6d2a4fe8ad5f5383424f934d |
| institution | OA Journals |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-9daab3cd6d2a4fe8ad5f5383424f934d2025-08-20T02:17:56ZengBMCCell Communication and Signaling1478-811X2024-10-0122112010.1186/s12964-024-01880-8Alternative splicing in ovarian cancerLiwei Wei0Yisheng Li1Jiawang Chen2Yuanmei Wang3Jianmin Wu4Huanming Yang5Yi Zhang6Medical School, Faculty of Medicine, Tianjin UniversityCollege of Pharmacy, Zhejiang University of TechnologyOujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain HealthHIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesAbstract Ovarian cancer is the second leading cause of gynecologic cancer death worldwide, with only 20% of cases detected early due to its elusive nature, limiting successful treatment. Most deaths occur from the disease progressing to advanced stages. Despite advances in chemo- and immunotherapy, the 5-year survival remains below 50% due to high recurrence and chemoresistance. Therefore, leveraging new research perspectives to understand molecular signatures and identify novel therapeutic targets is crucial for improving the clinical outcomes of ovarian cancer. Alternative splicing, a fundamental mechanism of post-transcriptional gene regulation, significantly contributes to heightened genomic complexity and protein diversity. Increased awareness has emerged about the multifaceted roles of alternative splicing in ovarian cancer, including cell proliferation, metastasis, apoptosis, immune evasion, and chemoresistance. We begin with an overview of altered splicing machinery, highlighting increased expression of spliceosome components and associated splicing factors like BUD31, SF3B4, and CTNNBL1, and their relationships to ovarian cancer. Next, we summarize the impact of specific variants of CD44, ECM1, and KAI1 on tumorigenesis and drug resistance through diverse mechanisms. Recent genomic and bioinformatics advances have enhanced our understanding. By incorporating data from The Cancer Genome Atlas RNA-seq, along with clinical information, a series of prognostic models have been developed, which provided deeper insights into how the splicing influences prognosis, overall survival, the immune microenvironment, and drug sensitivity and resistance in ovarian cancer patients. Notably, novel splicing events, such as PIGV|1299|AP and FLT3LG|50,941|AP, have been identified in multiple prognostic models and are associated with poorer and improved prognosis, respectively. These novel splicing variants warrant further functional characterization to unlock the underlying molecular mechanisms. Additionally, experimental evidence has underscored the potential therapeutic utility of targeting alternative splicing events, exemplified by the observation that knockdown of splicing factor BUD31 or antisense oligonucleotide-induced BCL2L12 exon skipping promotes apoptosis of ovarian cancer cells. In clinical settings, bevacizumab, a humanized monoclonal antibody that specifically targets the VEGF-A isoform, has demonstrated beneficial effects in the treatment of patients with advanced epithelial ovarian cancer. In conclusion, this review constitutes the first comprehensive and detailed exposition of the intricate interplay between alternative splicing and ovarian cancer, underscoring the significance of alternative splicing events as pivotal determinants in cancer biology and as promising avenues for future diagnostic and therapeutic intervention.https://doi.org/10.1186/s12964-024-01880-8Ovarian cancerAlternative splicingTumorigenesisSplicing variantsSplicing factorsBioinformatics |
| spellingShingle | Liwei Wei Yisheng Li Jiawang Chen Yuanmei Wang Jianmin Wu Huanming Yang Yi Zhang Alternative splicing in ovarian cancer Cell Communication and Signaling Ovarian cancer Alternative splicing Tumorigenesis Splicing variants Splicing factors Bioinformatics |
| title | Alternative splicing in ovarian cancer |
| title_full | Alternative splicing in ovarian cancer |
| title_fullStr | Alternative splicing in ovarian cancer |
| title_full_unstemmed | Alternative splicing in ovarian cancer |
| title_short | Alternative splicing in ovarian cancer |
| title_sort | alternative splicing in ovarian cancer |
| topic | Ovarian cancer Alternative splicing Tumorigenesis Splicing variants Splicing factors Bioinformatics |
| url | https://doi.org/10.1186/s12964-024-01880-8 |
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