Alternative Splicing in Tumorigenesis and Cancer Therapy
Alternative splicing (AS) is a pivotal post-transcriptional mechanism that expands the functional diversity of the proteome by enabling a single gene to generate multiple mRNA and protein isoforms. This process, which involves the differential inclusion or exclusion of exons and introns, is tightly...
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MDPI AG
2025-05-01
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| author | Huiping Chen Jingqun Tang Juanjuan Xiang |
| author_facet | Huiping Chen Jingqun Tang Juanjuan Xiang |
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| description | Alternative splicing (AS) is a pivotal post-transcriptional mechanism that expands the functional diversity of the proteome by enabling a single gene to generate multiple mRNA and protein isoforms. This process, which involves the differential inclusion or exclusion of exons and introns, is tightly regulated by splicing factors (SFs), such as serine/arginine-rich proteins (SRs), heterogeneous nuclear ribonucleoproteins (hnRNPs), and RNA-binding motif (RBM) proteins. These factors recognize specific sequences, including 5′ and 3′ splice sites and branch points, to ensure precise splicing. While AS is essential for normal cellular function, its dysregulation is increasingly implicated in cancer pathogenesis. Aberrant splicing can lead to the production of oncogenic isoforms that promote tumorigenesis, metastasis, and resistance to therapy. Furthermore, such abnormalities can cause the loss of tumor-suppressing activity, thereby contributing to cancer development. Importantly, abnormal AS events can generate neoantigens, which are presented on tumor cell surfaces via major histocompatibility complex (MHC) molecules, suggesting novel targets for cancer immunotherapy. Additionally, splice-switching oligonucleotides (SSOs) have shown promise as therapeutic agents because they modulate splicing patterns to restore normal gene function or induce tumor-suppressive isoforms. This review explores the mechanisms of AS dysregulation in cancer, its role in tumor progression, and its potential as a therapeutic target. We also discuss innovative technologies, such as high-throughput sequencing and computational approaches, that are revolutionizing the study of AS in cancer. Finally, we address the challenges and future prospects of targeting AS for personalized cancer therapies, emphasizing its potential in precision medicine. |
| format | Article |
| id | doaj-art-3e027fab1ba947f28b5722f1d29ff9f2 |
| institution | Matheson Library |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-3e027fab1ba947f28b5722f1d29ff9f22025-06-25T13:33:04ZengMDPI AGBiomolecules2218-273X2025-05-0115678910.3390/biom15060789Alternative Splicing in Tumorigenesis and Cancer TherapyHuiping Chen0Jingqun Tang1Juanjuan Xiang2Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha 410013, ChinaHunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha 410013, ChinaHunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha 410013, ChinaAlternative splicing (AS) is a pivotal post-transcriptional mechanism that expands the functional diversity of the proteome by enabling a single gene to generate multiple mRNA and protein isoforms. This process, which involves the differential inclusion or exclusion of exons and introns, is tightly regulated by splicing factors (SFs), such as serine/arginine-rich proteins (SRs), heterogeneous nuclear ribonucleoproteins (hnRNPs), and RNA-binding motif (RBM) proteins. These factors recognize specific sequences, including 5′ and 3′ splice sites and branch points, to ensure precise splicing. While AS is essential for normal cellular function, its dysregulation is increasingly implicated in cancer pathogenesis. Aberrant splicing can lead to the production of oncogenic isoforms that promote tumorigenesis, metastasis, and resistance to therapy. Furthermore, such abnormalities can cause the loss of tumor-suppressing activity, thereby contributing to cancer development. Importantly, abnormal AS events can generate neoantigens, which are presented on tumor cell surfaces via major histocompatibility complex (MHC) molecules, suggesting novel targets for cancer immunotherapy. Additionally, splice-switching oligonucleotides (SSOs) have shown promise as therapeutic agents because they modulate splicing patterns to restore normal gene function or induce tumor-suppressive isoforms. This review explores the mechanisms of AS dysregulation in cancer, its role in tumor progression, and its potential as a therapeutic target. We also discuss innovative technologies, such as high-throughput sequencing and computational approaches, that are revolutionizing the study of AS in cancer. Finally, we address the challenges and future prospects of targeting AS for personalized cancer therapies, emphasizing its potential in precision medicine.https://www.mdpi.com/2218-273X/15/6/789alternative splicingcancerimmunotherapyneoantigensinnovative technologies |
| spellingShingle | Huiping Chen Jingqun Tang Juanjuan Xiang Alternative Splicing in Tumorigenesis and Cancer Therapy Biomolecules alternative splicing cancer immunotherapy neoantigens innovative technologies |
| title | Alternative Splicing in Tumorigenesis and Cancer Therapy |
| title_full | Alternative Splicing in Tumorigenesis and Cancer Therapy |
| title_fullStr | Alternative Splicing in Tumorigenesis and Cancer Therapy |
| title_full_unstemmed | Alternative Splicing in Tumorigenesis and Cancer Therapy |
| title_short | Alternative Splicing in Tumorigenesis and Cancer Therapy |
| title_sort | alternative splicing in tumorigenesis and cancer therapy |
| topic | alternative splicing cancer immunotherapy neoantigens innovative technologies |
| url | https://www.mdpi.com/2218-273X/15/6/789 |
| work_keys_str_mv | AT huipingchen alternativesplicingintumorigenesisandcancertherapy AT jingquntang alternativesplicingintumorigenesisandcancertherapy AT juanjuanxiang alternativesplicingintumorigenesisandcancertherapy |