Function and Regulation of MicroRNAs and Their Potential as Biomarkers in Paediatric Liver Disease

Calvopina, Diego A.; Coleman, Miranda A.; Lewindon, Peter; Ramm, Grant A.

doi:10.3390/ijms17111795

Cited by 32 publications

(30 citation statements)

References 188 publications

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“…If untreated, this damage can cause progressive conjugated hyperbilirubinemia, cirrhosis and hepatic failure [63]. The incidence of BA is approximately one in 10,000 births worldwide, but without therapeutic intervention, BA can be fatal within 2 years, with a median survival rate of eight months [64].…”

Section: Biliary Atresiamentioning

confidence: 99%

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

et al. 2017

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Cholangiopathies are a group of rare, devastating diseases that arise from damaged cholangiocytes, the cells that line the intra- and extra-hepatic bile ducts of the biliary epithelium. Cholangiopathies result in significant morbidity and mortality and are a major cause of liver transplantation. A better understanding of the underlying pathogenesis that influences cholangiocyte dysregulation and cholangiopathy progression is necessary, considering the dismal prognosis associated with these diseases. MicroRNAs are a class of small, non-coding RNAs that regulate post-transcriptional mRNA expression of specific genes. The role of microRNAs has expanded to include the initiation and development of many diseases, including cholangiopathies. Understanding microRNA regulation of cholangiopathies may provide diagnostic and therapeutic benefit for these diseases. In this review, the authors primarily focus on studies published within the last five years that help determine the diagnostic and therapeutic potential of microRNAs in cholangiopathies.

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Section: Biliary Atresiamentioning

confidence: 99%

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

et al. 2017

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“…Recent publications demonstrated that microRNAs played an important role in the development of liver fibrosis . MicroRNAs are small, non‐coding RNAs which regulate the expression of numerous target genes at both transcriptional and translational levels.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice

Liu

Huang

Niu

et al. 2018

Basic Clin Pharma Tox

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Liver fibrosis is a common symptom of non-alcoholic steatohepatitis (NASH) and a worldwide clinical issue. The miR-122/HIF-1α signalling pathway is believed to play an important role in the genesis of progressive fibrosis. Isochlorogenic acid B (ICAB), naturally isolated from Laggera alata, is verified to have antioxidative and hepatoprotective properties. The aim of this study was to investigate the effect of ICAB on liver fibrosis in NASH and its potential protective mechanisms. NASH was induced in a mouse model with a methionine- and choline-deficient (MCD) diet for 4 weeks, and ICAB was orally administered every day at three doses (5, 10 and 20 mg/kg). Pathological results indicated that ICAB significantly improved the pathological lesions of liver fibrosis. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic hydroxyproline (Hyp), cholesterol (CHO) and triglyceride (TG) were also significantly decreased by ICAB. In addition, ICAB inhibited hepatic stellate cells (HSCs) activation and the expressions of hepatic genes involved in liver fibrosis including LOX, TGF-β1, MCP-1, COL1α1 and TIMP-1. ICAB also attenuated liver oxidative stress through Nrf2 signalling pathway. What is more, the decreased levels of miR-122 and over-expression of hepatic HIF-1α could be reversed by ICAB treatment. These results simultaneously confirmed that ICAB had a significant protective effect on fibrosis in NASH by inhibiting oxidative stress via Nrf2 and suppressing multiple profibrogenic factors through miR-122/HIF-1α signalling pathway.

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“…[207][208][209][210] MiRNAs have also been extensively studied in liver disease and their roles reviewed in detail elsewhere. 211,212 To summarise, differential hepatic miRNA expression in animal 213 and human studies [214][215][216] has been shown in various liver disease aetiologies including viral hepatitis, fatty liver disease and alcoholic liver disease. MiRNAs appear to regulate gene expression in critical areas, including processes involved in hepatic fibrogenesis.…”

Section: Mirnas and Diseasementioning

confidence: 99%

“…113 Novel molecules, such as miRNAs, are being actively investigated for their diagnostic and such as viral hepatitis, hepatic fibrosis and HCC has been discussed extensively elsewhere. 211,212,215 In CHC and CHC-related HCC, preliminary studies of miRNAs have identified some promising candidates but these results require further validation. 239,240 To improve diagnostic accuracy, the development of panels of the most promising miRNA candidates are now being explored to differentiate disease severities and identify HCC.…”

Section: Introductionmentioning

confidence: 99%

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

Weis¹

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Identification of 5 miRNA candidates (miRNA-10a-5p, miRNA-10b-5p, miRNA101-3p, miRNA 22-3p and miRNA-27b-3p) in the serum of 136 patients with cirrhosis that are differentially expressed according to disease severity in compensated cirrhosis (n=30), cirrhosis with varices (n=30), cirrhosis with ascites ± varices (n=60), and cirrhosis with variceal bleeding (n=16). MiRNA panels were assembled to distinguish patients with specific complications with the following diagnostic performance: • Varices panel (miRNA-10b-5p + miRNA-101-3p) with an AUC of 0.78 (95% CI 0.66-0.90, p<0.001) • Ascites panel (miRNA-10a-5p + miRNA-146a-5p) with an AUC of 0.83 (95% CI 0.75-0.92, p<0.001) • Variceal bleeding panel (miRNA-10a-5p) with an AUC of 0.80 (95% CI 0.65-0.95, p<0.001) • Decompensation panel, grouping ascites and variceal bleeding patients (miRNA-10a-5p, miRNA-146a-5p + miRNA-423-3p) with an AUC of 0.78 (95% CI 0.70-0.86, p<0.001). Combining platelet count < 150 (x10 9 /L) 2 with the miRNA panels improved the performance of the Varices panel and the Ascites panel (with AUCs of 0.84 and AUC of 0.87, respectively). This thesis has identified several differentially-expressed miRNA candidates across a clinically relevant spectrum of CLD and assembled promising panels of miRNAs that warrant further investigation for their diagnostic potential. Preliminary efforts to explore the possible functional roles of 2 candidates in HCC were unrewarding but further studies can build on these findings by optimising experimental conditions, validating identified miRNA candidates, and testing the prognostic potential of validated miRNAs as clinically-useful non-invasive biomarkers.

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Function and Regulation of MicroRNAs and Their Potential as Biomarkers in Paediatric Liver Disease

Cited by 32 publications

References 188 publications

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

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