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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Review

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

Authors: Zhihui Dou, Dapeng Zhao, Xiaohua Chen, Caipeng Xu, Xiaodong Jin, Xuetian Zhang, Yupei Wang, Xiaodong Xie, Qiang Li, Cuixia Di, Hong Zhang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

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.
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Metadata
Title
Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation
Authors
Zhihui Dou
Dapeng Zhao
Xiaohua Chen
Caipeng Xu
Xiaodong Jin
Xuetian Zhang
Yupei Wang
Xiaodong Xie
Qiang Li
Cuixia Di
Hong Zhang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-02001-w

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