Serum miR-21 and miR-26a Levels Negatively Correlate with Severity of Cirrhosis in Patients with Chronic Hepatitis B

Author(s): Shili Jiang*, Wei Jiang, Ying Xu, Xiaoning Wang, Yongping Mu, Ping Liu

Journal Name: MicroRNA

Volume 8 , Issue 1 , 2019

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Graphical Abstract:


Background and Objective: Accurately evaluating the severity of liver cirrhosis is essential for clinical decision making and disease management. This study aimed to evaluate the value of circulating levels of microRNA (miR)-26a and miR-21 as novel noninvasive biomarkers in detecting severity of cirrhosis in patients with chronic hepatitis B.

Methods: Thirty patients with clinically diagnosed chronic hepatitis B-related cirrhosis and 30 healthy individuals were selected. The serum levels of miR-26a and miR-21 were quantified by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of the miRNAs for detecting the severity of cirrhosis.

Results: Serum miR-26a and miR-21 levels were found to be significantly downregulated in patients with severe cirrhosis scored at Child-Pugh class C in comparison to healthy controls (miR-26a p<0.01, and miR-21 p<0.001, respectively). The circulating miR-26a and miR-21 levels in patients were positively correlated with serum albumin concentration but negatively correlated with serum total bilirubin concentration and prothrombin time. Receiver operating characteristic curve analysis revealed that both serum miR-26a and miR-21 levels were associated with a high diagnostic accuracy for patients with cirrhosis scored at Child-Pugh class C (miR-26a Cut-off fold change at ≤0.4, Sensitivity: 84.62%, Specificity: 89.36%, P<0.0001; miR-21 Cut-off fold change at ≤0.6, Sensitivity: 84.62%, Specificity: 78.72%, P<0.0001).

Conclusion: Our results indicate that the circulating levels of miR-26a and miR-21 are closely related to the extent of liver decompensation, and the decreased levels are capable of discriminating patients with cirrhosis at Child-Pugh class C from the whole cirrhosis cases.

Keywords: Child-Pugh score, chronic hepatitis B, cirrhosis, liver, microRNAs, noninvasive biomarker.

Zhang S, Wang F, Zhang Z. Current advances in the elimination of hepatitis B in China by 2030. Front Med 2017; 11: 490-501.
Cholongitas E1, Papatheodoridis GV, Vangeli M, et al.Systematic review: the model for end-stage liver disease--should it replace Child-Pugh’s classification for assessing prognosis in cirrhosis? Aliment Pharmacol Ther 2005; 22: 1079-89.
Lambrecht J, Verhulst S, Mannaerts I, et al. Prospects in non-invasive assessment of liver fibrosis: liquid biopsy as the future gold standard? Biochim Biophys Acta 2018; 1864: 1024-36.
Liu G, Friggeri A, Yang Y, et al. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 2010; 207: 1589-97.
Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980-4.
Marquez RT, Bandyopadhyay S, Wendlandt EB, et al. Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans. Lab Invest 2010; 90: 1727-36.
Liang H, Xu C, Pan Z, et al. The antifibrotic effects and mechanisms of microRNA-26a action in idiopathic pulmonary fibrosis. Mol Ther 2014; 22: 1122-33.
Wei C, Kim IK, Kumar S, et al. NF-κB mediated miR-26a regulation in cardiac fibrosis. J Cell Physiol 2013; 228: 1433-42.
Bao S, Zheng J, Li N, et al. Serum microRNA levels as a noninvasive diagnostic biomarker for the early diagnosis of hepatitis B virus-related liver fibrosis. Gut Liver 2017; 11: 860-9.
Rubiś P, Totoń-Żurańska J, Wiśniowska-Śmiałek S, et al. Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy. Int J Cardiol 2017; 231: 201-6.
Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 2009; 182: 4994-5002.
Gabriely G, Wurdinger T, Kesari S, et al. MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol 2008; 28: 5369-80.
Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007; 133: 647-58.
Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008; 27: 2128-36.
Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 2009; 361: 1437-47.
Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci US 2008; 105: 10513-8.
Chen J, Zhang K, Xu Y, et al. The role of microRNA-26a in human cancer progression and clinical application. Tumour Biol 2016; 37: 7095-108.
Zhuang C, Jiang W, Huang D, et al. Serum miR-21, miR-26a and miR-101 as potential biomarkers of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2016; 40: 386-96.
Padgett KA, Lan RY, Leung PC, et al. Primary biliary cirrhosis is associated with altered hepatic microRNA expression. J Autoimmun 2009; 32: 246-53.
Wu K, Li L, Li S. Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies. Tumour Biol 2015; 36: 1973-81.
Li G, Shen Q, Li C, et al. Identification of circulating MicroRNAs as novel potential biomarkers for hepatocellular carcinoma detection: a systematic review and meta-analysis. Clin Transl Oncol 2015; 17: 684-93.
Wang H, Hou L, Li A, et al. Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma. BioMed Res Int 2014; 2014: 864894.
Sohn W, Kim J, Kang SH, et al. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med 2015; 47: e184.
Bihrer V, Waidmann O, Friedrich-Rust M, et al. Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma. PLoS One 2011; 6: e26971.
Xu J, Wu C, Che X, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog 2011; 50: 136-42.
Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 2010; 56: 1830-8.
Appourchaux K, Dokmak S, Resche-Rigon M, et al. MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C. Sci Rep 2016; 6: 34935.

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Article Details

Year: 2019
Published on: 27 November, 2018
Page: [86 - 92]
Pages: 7
DOI: 10.2174/2211536607666180821162850
Price: $65

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