Aberrant Regulation of Alternative Pre-mRNA Splicing in Hepatocellular Carcinoma
Aberrant Regulation of Alternative Pre-mRNA Splicing in Hepatocellular Carcinoma
复制标题
肝细胞癌中选择性前 mRNA 剪接的异常调节
DOI：
10.1615/critreveukaryotgeneexpr.2014007702
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发表时间：
2014-01-01
影响因子：
1.6
通讯作者：
Zhu, Fan
中科院分区：
文献类型：
--
作者：
Liu, Lijuan;Xie, Shuixiang;Zhu, Fan
前体信使RNA（pre-mRNA）的选择性剪接通常用于增加正常多细胞生物体中基因组表达的信使RNA的多样性。选择性剪接的失调是包括癌症在内的许多人类疾病的基础。越来越多的证据支持这一广泛的基因调控层在肝癌发生中的重要作用。肝细胞癌（HCC）是世界上最致命的恶性肿瘤之一，因为它的侵袭性和有限的治疗选择。研究表明，异常的选择性剪接促进肝癌中致癌变异体的产生，而肝癌中的肿瘤抑制因子通过异常的选择性剪接而自我失活。此外，同一基因的不同剪接变体在HCC中可显示不同的甚至拮抗的生物学功能。因此，抑制致癌变异体的剪接和肿瘤抑制因子的自失活可能是新的治疗策略。这篇综述提供了一个新的证据的角度来看，选择性剪接作为一个关键的机制，为肝癌的发展和潜在的串扰通过不同的变异之间的信号通路可能有助于发展新的分子靶点的肝癌。
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.