Liu Lijuan, Xie Shuixiang, Zhang Chuanjie, Zhu Fan
Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan, P. R. China.
Department of Pathogenic Biology, Gannan Medical University, Jiangxi, P. R. China.
Crit Rev Eukaryot Gene Expr. 2014;24(2):133-49. doi: 10.1615/critreveukaryotgeneexpr.2014007702.
Alternative splicing of precursors messenger RNA (pre-mRNA) is commonly used to increase the diversity of messenger RNAs expressed by the genome in normal multicellular organisms. Dysregulation of alternative splicing underlies a number of human diseases, including cancers. Increasing evidence supports the important role of this expansive layer of gene regulation in hepatocarcinogenesis. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of its aggressive property and limited therapeutic options. Studies suggest that aberrant alternative splicing promotes generation of oncogenic variants in HCC, whereas tumor suppressors are self-inactivated by aberrant alternative splicing in HCC. Moreover, different spliced variants of the same gene can display distinct and even antagonistic biological functions in HCC. As a result, inhibiting the splicing of oncogenic variants and the self-inactivation of tumor suppressors are likely to be new therapy strategies. This review provides a perspective of the emerging evidence of both alternative splicing as a critical mechanism for the development of HCC and that potential cross-talk through signaling pathways among different variants might aid in the development of novel molecular targets of HCC.
前体信使核糖核酸（pre-mRNA）的可变剪接通常用于增加正常多细胞生物中基因组所表达信使核糖核酸的多样性。可变剪接失调是包括癌症在内的多种人类疾病的基础。越来越多的证据支持这一广泛的基因调控层面在肝癌发生过程中的重要作用。肝细胞癌（HCC）因其侵袭性和有限的治疗选择，是全球最致命的恶性肿瘤之一。研究表明，异常可变剪接促进了HCC中致癌变体的产生，而肿瘤抑制因子在HCC中因异常可变剪接而自我失活。此外，同一基因的不同剪接变体在HCC中可表现出不同甚至拮抗的生物学功能。因此，抑制致癌变体的剪接和肿瘤抑制因子的自我失活可能是新的治疗策略。本综述提供了一个观点，即可变剪接作为HCC发生发展的关键机制的新证据，以及不同变体之间通过信号通路的潜在相互作用可能有助于开发HCC的新型分子靶点。
