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.
Highlights
MicroRNAs are a class of highly conserved, chemically stable, small noncoding endogenous RNA (∼22 nt) molecules
In hepatitis B patients, the results have shown that miR-223 is elevated in serum from patients with chronic hepatitis B to a similar extent as in patients with hepatocellular carcinoma (HCC), suggesting the strong potential of miR-223 to serve as a novel biomarker for liver injury but not for HCC47
Bone marrow-derived mesenchymal stem cell (BMSC)-secreted miR-223-containing exosomes (BMSC-exo) prevent liver injury in an autoimmune hepatitis mouse model by suppressing hepatic NLR protein 3 (NLRP3) and caspase 1, and modification of miR-223 further improves its therapeutic efficacy against autoimmune hepatitis[86]
Summary
Studies have demonstrated that miRNA expression signatures are highly tissue- and disease-specific, and approximately 70% of miRNAs in the whole body have been discovered in liver tissues[8]. A different Dicer1-knockout mouse model, in which Dicer[1] is conditionally deleted in mature hepatocytes, fetal stagespecific genes are persistently expressed, resulting in increased hepatocyte proliferation and apoptosis, as well as spontaneous development of hepatocellular carcinoma (HCC)[10]. These data demonstrate that miRNAs have critical roles in hepatic physiology and pathology. By using smiR-223 derived from pre-miR-223 as a model, researchers further showed that smiR-223 cannot directly regulate mRNA activity through mRNA translational repression, it can interfere with the ability of miR-223 to mediate gene silencing either through mRNA cleavage or mRNA translational repression[25]. This condition implies the ability of miR-223 to provide an additional layer of control over miR-223 activity
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