期刊
CANCER LETTERS
卷 501, 期 -, 页码 83-104出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.11.043
关键词
Alternative splicing; Splicing factors; Hallmarks of cancer; Transcriptional modification; Post-transcriptional modification; Therapeutic targets
类别
资金
- National Natural Science Fund of China [81871916, 81672330]
- Excellent Backbone Plan of Zhongshan Hospital [2019ZSGG08]
More than 95% of human genes undergo alternative splicing, driving the generation and maintenance of cancer hallmarks. Splicing factors play crucial roles in the process, and targeted therapeutic strategies show promising prospects.
More than 95% of all human genes are alternatively spliced after transcription, which enriches the diversity of proteins and regulates transcript and/or protein levels. The splicing isoforms produced from the same gene can manifest distinctly, even exerting opposite effects. Mounting evidence indicates that the alternative splicing (AS) mechanism is ubiquitous in various cancers and drives the generation and maintenance of various hallmarks of cancer, such as enhanced proliferation, inhibited apoptosis, invasion and metastasis, and angiogenesis. Splicing factors (SFs) play pivotal roles in the recognition of splice sites and the assembly of spliceosomes during AS. In this review, we mainly discuss the similarities and differences of SF domains, the details of SF function in AS, the effect of SF-driven pathological AS on different hallmarks of cancer, and the main drivers of SF expression level and subcellular localization. In addition, we briefly introduce the application prospects of targeted therapeutic strategies, including small-molecule inhibitors, siRNAs and splice-switching oligonucleotides (SSOs), from three perspectives (drivers, SFs and pathological AS). Finally, we share our insights into the potential direction of research on SF-centric AS-related regulatory networks.
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