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  • Recent studies have analyzed the miRNA profile of

    2019-04-11

    Recent studies have analyzed the miRNA profile of serum and bile samples from patients with PSC and patients with CCA complicating PSC. Overall, the miRNA expression of all analyzed miRNAs from both patients with PSC and patients with CCA complicating PSC was significantly higher compared with healthy samples. Furthermore, miRNA concentrations in both serum and bile were increased in patients with CCA complicating PSC compared to levels in patients with PSC alone. The researchers also analyzed whether miRNA profiles differed between PSC alone and CCA complicating PSC patients and found that there were increased serum levels of miR-1281, miR-126, miR-122, miR-26a and miR-30b in PSC patients compared to CCA complicating PSC patients. These miRNAs, aside from miR-122, are mostly unstudied in liver pathology, but some studies have been reported on their functions. MiR-1281 is decreased during LDE225 cancer; miR-126 inhibits non-small cell lung carcinoma invasion; miR-122 aids in hepatocyte differentiation to reduce hepatocellular carcinoma formation; miR-26a inhibits the proliferation and invasion of cervical cancer cells; and miR-30b suppresses the formation of colorectal cancer. Interestingly, these upregulated miRNAs appear to all play a role in the inhibition of cancer formation, which may explain why they are upregulated in PSC alone patients versus CCA complicating PSC patients. Examination of the expression of miRNAs in bile revealed significantly increased concentrations of miR-412, miR-640, miR-1537 and miR-3189 in PSC alone patients compared with CCA complicating PSC patients. Similar to the upregulated miRNAs in serum, these miRNAs are largely unstudied in the liver. However, previously published data identifies miR-412 as upregulated in patients with ischemic hepatitis and patients with acetaminophen hepatotoxicity; miR-640 decreases angiogenesis in endothelial cells; miR-1537 is decreased in neuroblastoma; and miR-3189 plays an anti-tumoral role during glioblastoma. Similar to the above miRNAs, miR-1537 and miR-3189 may act as tumor suppressors, which explains why they are upregulated in PSC alone patients versus CCA complicating PSC patients. However, the role of miR-640 and miR-412 in these patient subsets is unclear. Similar research from another group analyzed serum miRNA levels in healthy control and PSC patient samples. Differential levels of 667 miRNAs were noted in diseased serum samples compared with healthy samples; however, no differences in miRNA expression were noted between different disease stages. From the 667 differentially expressed miRNAs, receiver operating characteristic (ROC) curves were analyzed to identify useful biomarkers. Following ROC analysis, a total of 21 differentially expressed miRNAs were noted as potential biomarkers of PSC compared with healthy controls. Furthermore, miR-200c was found to be decreased specifically in serum from PSC patients versus healthy controls. The results also demonstrated upregulation of miR-193b, miR-122 and miR-885-5p in serum from PSC patients compared with healthy controls. From this study, potential miRNA-based, PSC diagnostic tools were further identified. Work from another group of researchers analyzed miRNA expression profiles between PSC patients and healthy controls, but looked specifically at hepatic expression. This publication noted increased hepatic expression of miR-378a-5p in PSC patients compared with healthy controls. This paper further identified sulphotransferase 2A1 (SULT2A1), generally suggested to be a hepatoprotective protein, as a target of miR-378a-5p. Based on these findings, the paper concluded that increased levels of miR-378a-5p leads to decreased SULT2A1 expression and a subsequent increase in hepatic damage. Unlike the previous studies, this publication aimed to understand the underlying cellular pathway that regulates PSC-associated hepatic damage. These results suggest that targeting miR-378-5p or SULT2A1 could provide therapeutic benefit to patients suffering from PSC.