Department of Endocrinology and Metabolism, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China.
Exp Mol Med. 2018 Sep 26;50(9):1-12. doi: 10.1038/s12276-018-0153-7.
MiRNAs are small, noncoding RNAs, which can regulate gene expression posttranscriptionally, and they have emerged as key factors in disease biology by aiding in disease development and progression. MiR-223 is highly conserved during evolution and it was first described as a modulator of hematopoietic lineage differentiation. MiR-223 has an essential part in inflammation by targeting the nuclear factor-κB pathway and the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome. Recent studies have shown that miR-223 expression is deregulated in various types of liver diseases, including hepatitis virus infections, alcohol-induced liver injury, drug-induced liver injury, non-alcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma. As inflammatory and immune factors are involved in the occurrence and progress of liver diseases, deregulated miR-223 may participate in the pathogenesis of these conditions by influencing neutrophil infiltration, macrophage polarization, and inflammasome activation. This review first summarizes the present understanding of the biological functions of miR-223, including its gene location and transcription regulation, as well as its physiological role in hematopoietic differentiation. This review then focuses on the role of miR-223 in liver pathophysiology and its potential applications as a diagnostic biomarker and therapeutic target in liver diseases.
miRNAs 是小的非编码 RNA,可以在后转录水平上调节基因表达,它们通过帮助疾病的发生和发展,成为疾病生物学中的关键因素。miR-223 在进化过程中高度保守,最初被描述为造血谱系分化的调节剂。miR-223 通过靶向核因子-κB 途径和核苷酸结合寡聚结构域样受体蛋白 3 炎性小体,在炎症中起着重要作用。最近的研究表明,miR-223 的表达在各种类型的肝病中失调,包括肝炎病毒感染、酒精性肝损伤、药物性肝损伤、非酒精性脂肪性肝病、肝硬化和肝细胞癌。由于炎症和免疫因素参与了肝病的发生和进展,失调的 miR-223 可能通过影响中性粒细胞浸润、巨噬细胞极化和炎性小体激活来参与这些疾病的发病机制。本综述首先总结了目前对 miR-223 的生物学功能的理解,包括其基因位置和转录调控,以及其在造血分化中的生理作用。本综述然后重点介绍了 miR-223 在肝脏病理生理学中的作用及其作为肝脏疾病诊断生物标志物和治疗靶点的潜在应用。