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.
酒精相关性肝病（ALD）是发达国家慢性肝病及肝细胞癌（HCC）发生的主要病因，已成为重大公共卫生问题。目前除肝移植或HCC肿瘤切除术外，ALD与HCC的治疗手段极为有限。因此，解析这些疾病发生发展的分子机制对于发现早期生物标志物、设计有效治疗方案具有重要意义。越来越多的证据表明，表观遗传学改变在ALD和HCC的发展过程中发挥核心作用。其中，microRNA通过在转录后水平调控参与肝脏代谢、炎症反应、纤维化及致癌过程的多个基因表达，对该疾病进程产生重要影响。本文综述了当前关于miRNA在ALD不同阶段的功能及其在癌变进展中作用的研究进展，指出ALD各阶段均存在与肝癌发生相关的miRNA表达失调现象，这些miRNA可视为HCC的启动因子。通过生物信息学分析，我们发现了多个可能参与HCC发生的新型miRNA。最后，本文探讨了靶向miRNA治疗这些疾病的潜在临床应用价值。
肿瘤(癌症)患者之家