Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation

Bcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers...

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Bibliographic Details
Published in:Journal of experimental & clinical cancer research 2021-06, Vol.40 (1), p.194-194, Article 194
Main Authors: Dou, Zhihui, Zhao, Dapeng, Chen, Xiaohua, Xu, Caipeng, Jin, Xiaodong, Zhang, Xuetian, Wang, Yupei, Xie, Xiaodong, Li, Qiang, Di, Cuixia, Zhang, Hong
Format: Article
Language:English
Subjects:
Adapter proteins
Alternative Splicing
Animals
Apoptosis
Apoptosis - physiology
Bcl-x
bcl-X Protein - metabolism
Binding sites
Cancer
Cell apoptosis
Development and progression
DNA damage
DNA methylation
Epigenetic inheritance
Epigenetics
Genes
Health aspects
Humans
Messenger RNA
Mutation
Neoplasms - genetics
Protein Isoforms
Review
RNA polymerase
Small molecular modulators
Splice-switching oligonucleotides
Splicing correction
Transcription factors
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Summary:Bcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.
ISSN:1756-9966
0392-9078
1756-9966
DOI:10.1186/s13046-021-02001-w