Jouve Mickaël, Carpentier Rodolphe, Kraiem Sarra, Legrand Noémie, Sobolewski Cyril
Univ. Lille, Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, F-59000 Lille, France.
Cancers (Basel). 2023 Nov 23;15(23):5557. doi: 10.3390/cancers15235557.
Alcohol-related Liver Disease (ALD) is the primary cause of chronic liver disorders and hepatocellular carcinoma (HCC) development in developed countries and thus represents a major public health concern. Unfortunately, few therapeutic options are available for ALD and HCC, except liver transplantation or tumor resection for HCC. Deciphering the molecular mechanisms underlying the development of these diseases is therefore of major importance to identify early biomarkers and to design efficient therapeutic options. Increasing evidence indicate that epigenetic alterations play a central role in the development of ALD and HCC. Among them, microRNA importantly contribute to the development of this disease by controlling the expression of several genes involved in hepatic metabolism, inflammation, fibrosis, and carcinogenesis at the post-transcriptional level. In this review, we discuss the current knowledge about miRNAs' functions in the different stages of ALD and their role in the progression toward carcinogenesis. We highlight that each stage of ALD is associated with deregulated miRNAs involved in hepatic carcinogenesis, and thus represent HCC-priming miRNAs. By using in silico approaches, we have uncovered new miRNAs potentially involved in HCC. Finally, we discuss the therapeutic potential of targeting miRNAs for the treatment of these diseases.
酒精性肝病(ALD)是发达国家慢性肝脏疾病和肝细胞癌(HCC)发生的主要原因,因此是一个重大的公共卫生问题。不幸的是,除了肝移植或HCC的肿瘤切除外,ALD和HCC几乎没有其他治疗选择。因此,阐明这些疾病发生发展的分子机制对于识别早期生物标志物和设计有效的治疗方案至关重要。越来越多的证据表明,表观遗传改变在ALD和HCC的发生发展中起着核心作用。其中,微小RNA通过在转录后水平控制多个参与肝脏代谢、炎症、纤维化和致癌作用的基因的表达,对这种疾病的发展起重要作用。在这篇综述中,我们讨论了关于微小RNA在ALD不同阶段的功能及其在致癌进程中的作用的现有知识。我们强调,ALD的每个阶段都与参与肝癌发生的失调微小RNA相关,因此这些微小RNA是引发HCC的微小RNA。通过计算机分析方法,我们发现了可能参与HCC的新的微小RNA。最后,我们讨论了以微小RNA为靶点治疗这些疾病的潜在治疗价值。