Serum microRNA-125a-5p, a useful biomarker in liver diseases, correlates with disease progression

Zheng, Jianjian; Zhou, Zhenxu; Li, Guojun; Dong, Peihong; Chen, Zhanguo; Lin, Dezhao; Chen, Bicheng; Yu, Fang

doi:10.3892/mmr.2015.3546

Cited by 34 publications

(21 citation statements)

References 28 publications

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“…Coppola et al [18] further indicated that liver miR-125a-5p is correlated with HBV replication and disease progression in chronic hepatitis B patients. Our previous study demonstrated that serum miR-125a-5p may be a non-invasive biomarker for predicting disease progression in human liver diseases [19]. Here we report that miR-125a-5p is up-regulated in mice with liver fibrosis and activated HSCs, in line with the results obtained in humans.…”

Section: Discussionsupporting

confidence: 81%

“…Compared with the control, an increased level of miR125a-5p was observed in liver fibrosis (Fig. 1D), consistent with previous results in humans [18,19].…”

Section: Mir-125a-5p Is Up-regulated In Liver Fibrosis and Activated supporting

confidence: 81%

“…In chronic hepatitis B patients, miR-125a-5p is correlated with hepatitis B virus (HBV) replication and disease progression [18]. Our previous study indicated that serum miR-125a-5p may predict disease progression in human liver diseases [19]. However, the biological role and underlying mechanism of miR-125a-5p in liver fibrosis requires further study.…”

Section: Introductionmentioning

confidence: 97%

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MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1

et al. 2016

Cell Physiol Biochem

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Key Words MicroRNA • MiR-125a-5p • Hepatic stellate cells • Liver fibrosis • FIH1Abstract Background/Aims: Emerging evidence shows that microRNAs (miRNAs) play a crucial role in the regulation of activation, proliferation and apoptosis of hepatic stellate cells (HSCs). Previous studies have indicated that miR-125a-5p is correlated with hepatitis B virus replication and disease progression. However, little is known about the biological role and underlying mechanism of miR-125a-5p in liver fibrosis. Methods: We analyzed the level of miR-125a-5p in carbon tetrachloride-induced liver fibrosis and activated HSCs. We analyzed the effects of miR-125a-5p down-regulation on HSC activation and proliferation. We also analyzed the binding of miR-125a-5p to the 3′-untranslated region of factor inhibiting hypoxia-inducible factor 1 (FIH1) mRNA. Results: Up-regulation of miR-125a-5p was observed in the liver tissues of fibrotic mice and activated HSCs. Down-regulation of miR-125a-5p prevented the activation and proliferation of HSCs. FIH1, a negative modulator of hypoxia inducible factor 1, was confirmed to be a target of miR-125a-5p using the luciferase reporter assay. Further studies demonstrated that miR-125a-5p prompted the activation and proliferation of HSCs, at least in part, by down-regulating FIH1. Conclusion: Our findings shed new light on miRNAs as a promising therapeutic target in liver fibrosis.G. Li and J. Li contributed equally to this work.

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Section: Discussionsupporting

confidence: 81%

“…Compared with the control, an increased level of miR125a-5p was observed in liver fibrosis (Fig. 1D), consistent with previous results in humans [18,19].…”

Section: Mir-125a-5p Is Up-regulated In Liver Fibrosis and Activated supporting

confidence: 81%

Section: Introductionmentioning

confidence: 97%

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MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1

et al. 2016

Cell Physiol Biochem

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“…MiR-125a-5p is also involved in lipid metabolism [ 91 ] and its level has been found increased in hyperlipidemic and/or hyperglycemic patients’ sera [ 92 ]. MiR-125a-5p serum levels have been also described as biomarkers in liver diseases [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice

et al. 2016

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BackgroundHepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Non-alcoholic fatty liver disease (NAFLD) is a frequent chronic liver disorder in developed countries. NAFLD can progress through the more severe non alcoholic steatohepatitis (NASH), cirrhosis and, lastly, HCC. Genetic and epigenetic alterations of coding genes as well as deregulation of microRNAs (miRNAs) activity play a role in HCC development. In this study, the C57BL/6J mouse model was long term high-fat (HF) or low-fat (LF) diet fed, in order to analyze molecular mechanisms responsible for the hepatic damage progression.MethodsMice were HF or LF diet fed for different time points, then plasma and hepatic tissues were collected. Histological and clinical chemistry assays were performed to assess the progression of liver disease. MicroRNAs’ differential expression was evaluated on pooled RNAs from tissues, and some miRNAs showing dysregulation were further analyzed at the individual level.ResultsCholesterol, low and high density lipoproteins, triglycerides and alanine aminotransferase increase was detected in HF mice. Gross anatomical examination revealed hepatomegaly in HF livers, and histological analysis highlighted different degrees and levels of steatosis, inflammatory infiltrate and fibrosis in HF and LF animals, demonstrating the progression from NAFLD through NASH. Macroscopic nodules, showing typical neoplastic features, were observed in 20 % of HF diet fed mice. Fifteen miRNAs differentially expressed in HF with respect to LF hepatic tissues during the progression of liver damage, and in tumors with respect to HF non tumor liver specimens were identified. Among them, miR-340-5p, miR-484, miR-574-3p, miR-720, whose expression was never described in NAFLD, NASH and HCC tissues, and miR-125a-5p and miR-182, which showed early and significant dysregulation in the sequential hepatic damage process.ConclusionsIn this study, fifteen microRNAs which were modulated in hepatic tissues and in tumors during the transition NAFLD-NASH-HCC are reported. Besides some already described, new and early dysregulated miRNAs were identified. Functional analyses are needed to validate the results here obtained, and to better define the role of these molecules in the progression of the hepatic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-2007-1) contains supplementary material, which is available to authorized users.

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“…For example, HCC patients with low levels of miR-665 showed a strong association with large tumour size (> 5 cm), local tumour invasion and metastases [74] ; Shi et al [75] showed that decreased levels of exosomal miR-638 had poor OS. Zheng et al [76] reported that low levels of serum miR-125a-5p were associated with a lower OS compared with those exhibiting higher expression levels, and more recently Liu et al [77] confirmed by a Kaplan-Meier analysis that HCC patients with lower serum miR-125b levels showed reduced time to recurrence and OS. Many studies involved the analysis of circulating miR-21.…”

Section: Circulating Mirnas For Hcc Prognosismentioning

confidence: 96%

Circulating tumor DNAs and non-coding RNAs as potential biomarkers for hepatocellular carcinoma diagnosis, prognosis and response to therapy

Guerriero¹,

Moshiri²,

Lupini³

et al. 2019

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide and despite improvement in therapeutic approaches, prognosis remains poor. This can be partly attributed to the fact that the majority of HCCs are diagnosed at intermediate or advanced stages. Availability of circulating biomarkers able to detect HCC at early stages could improve patients' prognosis. At present, however, alpha fetoprotein or desg-carboxyprothrombin are unable to reliably detect HCC at early stages and better circulating biomarkers are needed. Circulating tumor DNA (ctDNA) and non-coding RNAs (ncRNAs) are emerging as promising biomarkers to achieve the goal. Genetic and epigenetic alterations in ctDNA allow to pinpoint tumor-specific biomarkers, reveal tumor heterogeneity, help monitor tumor evolution over time and assess therapy efficacy. It remains to be fully evaluated the possibility of detecting these biomarkers at early tumor stages. Circulating ncRNAs are quantitative biomarkers with potential use in diagnostic, prognostic and predictive clinical settings. They may help to reveal HCC at early stages. However, because of heterogeneous and sometimes conflicting reported results, they still require validation and standardization of pre-analytical and analytical approaches before clinical applications could be envisaged.

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Serum microRNA-125a-5p, a useful biomarker in liver diseases, correlates with disease progression

Abstract: Abstract. It has be en demonst rated t hat l iver microRNA-125a-5p (miR-125a-

Cited by 34 publications

References 28 publications

MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1

MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1

MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice

Circulating tumor DNAs and non-coding RNAs as potential biomarkers for hepatocellular carcinoma diagnosis, prognosis and response to therapy

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