Li Hai-Di, Du Xiao-Sa, Huang Hui-Min, Chen Xin, Yang Yang, Huang Cheng, Meng Xiao-Ming, Li Jun
The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.
The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, China.
J Cell Physiol. 2019 Sep;234(9):14709-14720. doi: 10.1002/jcp.28229. Epub 2019 Jan 31.
Alcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA-122 is a marker of hepatocyte damage, and miRNA-155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome-derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.
酒精性肝病(ALD)是一个发病率很高的复杂过程,可导致肝功能障碍,其包含广泛的肝脏病变,包括脂肪性肝炎、纤维化、肝硬化,最终发展为肝细胞癌。迄今为止,ALD的分子机制尚未完全阐明,且仍缺乏有效的治疗方法。大量证据表明,非编码RNA(ncRNA),特别是微小RNA(miRNA)的失调与ALD的病因及进展相关,包括肝细胞损伤、脂质代谢紊乱、强烈的炎症反应、氧化应激、程序性细胞死亡、纤维化以及酒精诱导的表观遗传变化。例如,循环miRNA-122是肝细胞损伤的标志物,而miRNA-155是炎症的潜在标志物,表明它们在ALD诊断治疗方面的潜力。此外,长链非编码RNA(lncRNA)和环状RNA在ALD中的作用也正在被揭示。此外,循环ncRNA和外泌体来源的ncRNA最近受到了更多关注,提示其在ALD预防和治疗中的作用。本综述涵盖了ncRNA在ALD中的作用,以及作为诊断标志物和治疗选择的潜在用途。