Role of miR-223 in the pathophysiology of liver diseases

Abstract

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.

Fig. 1. MiR-223 has important roles in normal physiology and hepatic pathogenesis.

MiR-223 is located within the q12 locus of the X chromosome and is regulated by several transcription factors, epigenetic modification, and smiR-223. MiR-223 has important roles in physiological condition, including hematopoietic differentiation, osteoclastogenesis, embryonic stem cell (ESC) differentiation, cell apoptosis, chromosomal stability, hepatic cholesterol metabolism, and hepatic drug metabolism. MiR-223 is also involved in the pathogenesis of various liver diseases by influencing immune cell differentiation, neutrophil infiltration, macrophage polarization, inflammasome activation, iron homeostasis, metabolic signaling pathways, and inflammatory signaling pathways