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Introduction
Tuberculosis (TB), which is a chronic infectious disease caused by Mycobacterium tuberculosis, is a global burden, with 8.7 million new cases and 1.4 million mortalities reported in 2011 (1). Anti-TB drug-induced liver injury (ADLI) is a severe adverse effect of TB treatment and may negatively affect treatment compliance.
Isoniazid (INH) is a first-line therapy for the treatment of TB, however, hepatotoxicity is a frequently observed side effect of INH that may progress into liver cirrhosis (2).
The current biomarkers for liver injury [serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] are adequate indicators of damage or altered liver function (3). However, the aforementioned parameters are unable to conclusively identify liver injury. In addition, serum ALT and AST activity also increase following the injury of other organs, and therefore are not selective for liver injury (4). Thus, gene expression variations are preferable for the classification of hepatotoxicants (5). Our previous study used epigenetics to identify that DNA methylation is a more sensitive marker for the detection of ADLI (6). Furthermore, recent studies have revealed that microRNA (miRNA/miR) may be used as a novel biomarker for mRNA regulatory genes (7,8).
miRNAs are small (18–25 nt) endogenous, non-coding RNA molecules that regulate post-transcriptional gene expression through RNA interference, or through inhibition of translational initiation and progression (9). Over 30% of mammalian genes are regulated by miRNA (10); therefore, miRNAs are important in a wide variety of physiological and pathological processes (11). It has been reported that miRNA expression levels differ significantly in various diseases, indicating the potential for their use as biomarkers (12–14).
Among miRNAs, miR-122, which accounts for ~70% of the total miRNA in the adult liver, is associated with liver biology and disease, including cell cycle progression, hepatocellular carcinogenesis (15), lipid metabolism (16) and fibrosis (17). Furthermore, miR-122 has been confirmed as a potential biomarker for the diagnosis of hepatotoxicity caused by acetaminophen (18) and alcohol (19). In addition, miR-155 is a multi-functional miRNA known to have a regulatory role in numerous biological processes, including immunity (20), inflammation (21), atherosclerosis (22) and cancer (23). However, it has been demonstrated that liver tissue miR-155 expression levels are increased in non-alcoholic steatohepatitis and hepatocellular carcinoma, and the expression levels were associated with disease severity (24,25). These...