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Serum microRNA 143 as a potential biomarker for the diagnosis of hepatitis C virus-related hepatocellular carcinoma
The Egyptian Journal of Internal Medicine volume 31, pages 214–221 (2019)
Abstract
Background
Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide. Early recognition of the onset of HCC would help to select more effective therapies for patients leading to a better prognosis and life span. So, the development of effective markers for the diagnosis of HCC could have an impact on HCC-related cancer mortality. MicroRNAs (miRNAs) are reported as a group of small noncoding RNAs that can function as endogenous RNA interference to regulate the expression of targeted genes.
Aim
To study serum miR-143 expression level in patients with hepatitis C virus (HCV)-related HCC.
Patients and methods
The present study was conducted on 60 participants classified into group A: 30 patients with HCV-related cirrhosis with HCC; group B: 15 patients with HCV-related cirrhosis without HCC; and group C: healthy participants as control. Expression of miR-143 in the serum of all participants was obtained in all groups. Total serum RNA was extracted with small RNA enrichment followed by reverse transcription real-time PCR. Expression of miR-143 in the serum of all participants was obtained using the comparative cycle threshold method (2–ΔΔCT) after normalization for the expression of Syn-cel-miR-39 mi script miRNA mimic as control. MiR-143 expression levels were then compared in different groups.
Results
The mean serum miR-143 levels were significantly higher in cirrhotic patients without and with HCC than in healthy participants (1.69±0.64, 13.0±6.23 vs. 0.56 ±0.29, P< 0.001, respectively) and in patients with HCC than in patients without HCC (P<0.001). The mean serum miR-143 levels were significantly higher in cirrhotic patients with HCC Barcelona Clinic Liver Cancer stage D than stage B (19.91±2.40, 13.41±1.80, P< 0.001, respectively) and in stage B compared with stage A (13.41±1.80, 5.68±1.86, P<0.001, respectively).
Conclusion
The significantly higher serum level of miR-143 in cirrhotic patients with HCC compared with those without and to normal participants may suggest its role in hepatocarcinogenesis and may have a value as a potential biomarker for early diagnosis of HCV- related HCC.
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. Cancer J Clin 2011; 61:69–90.
Stefaniuk P, Cianciara J, Wiercinska-Drapalo A. Present and future possibilities for early diagnosis of hepatocellular carcinoma. World J Gastroenterol 2010; 16:418–424.
Sun S, Poon RT, Lee NP, Yeung C, Chan KL, Ng IO, et al. Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors (<or=2 cm). J Proteome Res 2010; 9:1923–1930.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013; 495:384–388.
Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther 2009; 9:703–711.
Di Stefano V, Zaccagnini G, Capogrossi MC, Martelli F. microRNAs as peripheral blood biomarkers of cardiovascular disease. Vascul Pharmacol 2011; 55:111–118.
Luo J, Chen M, Huang H, Yuan T, Zhang M, Zhang K, et al. Circulating microRNA-122a as a diagnostic marker for hepatocellular carcinoma. Onco Targets Ther 2013; 6:577–583.
Trakooljul N, Hicks JA, Liu HC. Identification of target genes and pathways associated with chicken miR-143. Anim Genet 2010; 41:357–364.
Ng EK, Li R, Shin VY, Siu JM, Ma ES, Kwong A. MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumour Biol 2014; 35:2591–2598.
Naito Y, Sakamoto N, Oue N, Yashiro M, Sentani K, Yanagihara K, et al. MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer. Cancer Sci 2014; 105:228–235.
Schee K, Lorenz S, Worren MM, Gunther CC, Holden M, Hovig E, et al. Deep sequencing the MicroRNA transcriptome in colorectal cancer. PLoS One 2013; 8:e66165.
Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 2007; 297:1901–1908.
Fan X, Chen X, Deng W, Zhong G, Cai Q, Lin T. Upregulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression. BMC Cancer 2013; 13:61.
Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006; 25:2537–2545.
Abd Elmouttaleb AT, Abd-Elatif DM, Soliman GM, Taher MS, Abonar AA. Serum micro RNA-122 as a biomarker for hepatocellular carcinoma in chronic hepatitis C virus patients. Res Cancer Tumor 2015; 4:25–33.
Trebica J, Anadol E, Elfimova N, Roggendorf M, Viazov S, Wedemeyer I, et al. Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis. J Hepatol 2013; 58:234–239.
Sassen S, Eric A, Miska EA, Caldas C. MicroRNA-implications for cancer. Virchows Arch 2008; 452:1–10.
Zhu H, Han C, Wu T. MiR-17-92 cluster promotes hepatocarcinogenesis. Carcinogenesis 2015; 36:1213–1222.
Zhang X, Liu S, Hu T, He Y, Sun S. Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 2009; 50:490–499.
Zhang Z, Meng H, Wang N, Liang L, Liu L, Lu SM, et al. Serum micro RNA 143 and micro RNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol 2014; 9:135.
Shen S, Lin Y, Yuan X, Shen L, Chen J, Chen L, et al. Biomarker micro RNAs for diagnosis, prognosis and treatment of hepatocellular carcinoma: a functional survey and analysis. Sci Rep 2016; 6:38311.
Liu X, Gong J, Xu B. miR-143 down-regulates TLR2 expression in hepatoma cells and inhibits hepatoma cell proliferation and invasion. Int J Clin Exp Pathol 2015; 8:12738–12747.
Wang Y, Lu Z, Li Y, Ji D, Zhang P, Liu Q, et al. miR-143 inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of TLR2 expression. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2014; 30:1076–1079.
You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin?. Cancer Cell 2012; 22:9–20.
Ashworth A, Lord CJ, Reis-Filho JS. Genetic interactions in cancer progression and treatment. Cell 2011; 145:30–38.
Pogribny IP, Rusyn I. Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma. Cancer Lett 2014; 342:223–230.
Qi P, Cheng SQ, Wang H, Li N, Chen Y, Fand Gao CF. Serum microRNAs as biomarkers for hepatocellular carcinoma in chinese patients with chronic hepatitis B virus infection. PLoS ONE 2011; 6:e28486.
Mamdouh S, Khorshed F, Aboushousha T, Hamdy H, Diab A, Seleem M, et al. Evaluation of Mir-224, Mir-215 and Mir-143 as serum biomarkers in HCV associated hepatocellular carcinoma. Asian Pac J Cancer Prev 2017; 18:3167–3171.
Lin XJ, Chong Y, Guo ZW, Xie C, Yang XJ, Zhang Q, et al. A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study. Lancet Oncol 2015; 16:804–815.
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El-Gohary, A.M., Zeid, A.E., Ibrahim, M.E. et al. Serum microRNA 143 as a potential biomarker for the diagnosis of hepatitis C virus-related hepatocellular carcinoma. Egypt J Intern Med 31, 214–221 (2019). https://doi.org/10.4103/ejim.ejim_82_18
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DOI: https://doi.org/10.4103/ejim.ejim_82_18