Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer cases, with more than 850,000 new diagnoses per year globally. Recent trends in the United States have shown that liver cancer mortality has continued to increase in both men and women, while 5-year survival remains below 20%. Understanding key mechanisms that drive chronic liver disease progression to HCC can reveal new therapeutic targets and biomarkers for early detection of HCC. In that regard, many studies have underscored the importance of alternative splicing as a source of novel HCC prognostic markers and disease targets. Alternative splicing of pre-mRNA provides functional diversity to the genome, and endows cells with the ability to rapidly remodel the proteome. Genes that control fundamental processes, such as metabolism, cell proliferation, and apoptosis, are altered globally in HCC by alternative splicing. This review highlights the major splicing factors, RNA binding proteins, transcriptional targets, and signaling pathways that are of key relevance to HCC. We highlight primary research from the past 3–5 years involving functional interrogation of alternative splicing in rodent and human liver, using both large-scale transcriptomic and focused mechanistic approaches. Because this is a rapidly advancing field, we anticipate that it will be transformative for the future of basic liver biology, as well as HCC diagnosis and management.

肝细胞癌 (HCC) 占原发性肝癌病例的大部分，全球每年有超过 850,000 例新诊断。美国最近的趋势表明，男性和女性的肝癌死亡率持续上升，而 5 年生存率仍低于 20%。了解推动慢性肝病进展为 HCC 的关键机制可以揭示新的治疗靶点和早期检测 HCC 的生物标志物。在这方面，许多研究强调了选择性剪接作为新型 HCC 预后标志物和疾病靶标来源的重要性。前体 mRNA 的选择性剪接为基因组提供了功能多样性，并赋予细胞快速重塑蛋白质组的能力。控制基本过程的基因，例如新陈代谢、细胞增殖和凋亡，通过选择性剪接在 HCC 中全局改变。本综述重点介绍了与 HCC 相关的主要剪接因子、RNA 结合蛋白、转录靶点和信号通路。我们强调了过去 3-5 年的主要研究，涉及啮齿动物和人类肝脏中选择性剪接的功能询问，使用大规模转录组学和集中机制方法。由于这是一个快速发展的领域，我们预计它将为基础肝脏生物学以及 HCC 诊断和管理的未来带来变革。我们强调了过去 3-5 年的主要研究，涉及啮齿动物和人类肝脏中选择性剪接的功能询问，使用大规模转录组学和集中机制方法。由于这是一个快速发展的领域，我们预计它将为基础肝脏生物学以及 HCC 诊断和管理的未来带来变革。我们强调了过去 3-5 年的主要研究，涉及啮齿动物和人类肝脏中选择性剪接的功能询问，使用大规模转录组学和集中机制方法。由于这是一个快速发展的领域，我们预计它将为基础肝脏生物学以及 HCC 诊断和管理的未来带来变革。