Abstract
Recently, serum miRNAs have been evolved as possible biomarkers for different diseases including hepatocellular carcinoma and other types of cancers. Investigating certain serum miRNAs as novel non-invasive markers for early detection of HCV-positive cirrhosis and hepatocellular carcinoma (HCC). The expression profiles of 58 miRNA were analyzed in patient’s plasma of chronic hepatitis C (CHC), HCV-positive cirrhosis and HCV-positive HCC and compared with control group samples. Totally 94 plasma samples; 64 patient plasma (26 CHC, 30 HCV-positive cirrhosis, 8 HCV-positive HCC) and 28 control group plasma, were included. The expression profiles of 58 miRNAs were detected for all patient and control group plasma samples by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation) system. In CHC group, expression profiles of miR-30a-5p, miR-30c-5p, miR-206 and miR-302c-3p were found significantly deregulated (p < 0.05) when compared versus control group. In HCV-positive cirrhosis group, expression profiles of miR-30c-5p, miR-223-3p, miR-302c-3p, miR-17-5p, miR-130a-3p, miR-93-5p, miR-302c-5p and miR-223-3p were found significantly deregulated (p < 0.05). In HCV-positive HCC group, expression profiles of miR-17-5p, miR-223-3p and miR-24-3p were found significant (p < 0.05). When all groups were compared versus control, miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p were found significantly deregulated for cirrhosis and HCC. These results imply that miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive biomarkers of HCV-positive HCC in very early, even at cirrhosis stage of liver disease.
Similar content being viewed by others
References
Murakami Y, Tanaka M, Toyoda H, Hayashi K, Kuroda M, Tajima A, Shimotohno K (2010) Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C. BMC Med Genomics 3:48
Ferlay J, Bray F, Pisani P, Parkin DM (2004) GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide, version 2.0, IARC CancerBase No. 5. IARC Press, Lyon
Sun J, Haiqi LuH, Wang X, Jin H (2013) MicroRNAs in Hepatocellular Carcinoma: regulation, Function, and clinical implications. ScientificWorldJournal 2013:924206. doi:10.1155/2013/924206
Kremsdorf D, Soussan P, Paterlini-Brechot P, Brechot C (2006) Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis. Oncogene 25(27):3823–3833
Zhang Y, Wei W, Cheng N, Wang K, Li B, Jiang X, Sun S (2012) Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology 56:1631–1640
Dash S, Haque S, Joshi V, Prabhu R, Hazari S, Fermin C, Garry R (2005) HCV-hepatocellular carcinoma: new findings and hope for effective treatment. Microsc Res Tech 68:130–148
Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, Wang JF, Zhang Z, Lu S, Huang X, Wang Z, Qiu S, Wang X, Yang G, Sun H, Tang Z, Wu Y, Zhu H, Fan J (2011) Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol 29:4781–4788
Qi P, Cheng SQ, Wang H, Li N, Chen YF, Gao CF (2011) Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One 6(12):e28486
Ura S, Honda M, Yamashita T, Ueda T, Takatori H, Nishino R, Sunakozaka H, Sakai Y, Horimoto K, Kaneko S (2009) Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology 49:1098–1112
Etheridge A, Lee I, Hood L, Galas D, Wang K (2011) Extracellular microRNA: a new source of biomarkers. Mutat Res 717:85–90
Shwetha S, Gouthamchandra K, Chandra M, Ravishankar B, Khaja MN, Das S (2013) Circulating miRNA profile in HCV infected serum: novel insight into pathogenesis. Sci Rep 3:1555
Ishida H, Tatsumi T, Hosui A, Nawa T, Kodama T, Shimizu S, Hikita H, Hiramatsu N, Kanto T, Hayashi N, Takehara T (2011) Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway. Biochem Biophys Res Commun 412:92–97
Diaz G, Melis M, Tice A, Kleiner DE, Mishra L, Zamboni F, Farci P (2013) Identification of microRNAs specifically expressed in hepatitis C virus-associated hepatocellular carcinoma. Int J Cancer 133(4):819–824. doi:10.1002/ijc.28075
Gorur A, Balci Fidanci S, Dogruer Unal N, Ayaz L, Akbayir S, Yildirim Yaroglu H, Dirlik M, Serin MS, Tamer L (2012) Determination of plasma microRNA for early detection of gastric cancer. Mol Biol Rep 40(3):2091–2096. doi:10.1007/s11033-012-2267-7
Zinkin NT, Grall F, Bhaskar K, Otu HH, Spentzos D, Kalmowitz B, Wells M, Guerrero M, Asara JM, Libermann TA, Afdhal NH (2008) Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res 14:470–477
Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922
Chen Xian-Ming (2009) MicroRNA signatures in liver diseases. World J Gastroenterol 15:1665–1672
Nohata N, Hanazawa T, Enokida H, Seki N (2012) microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget 3:9–21
Lakner AM, Bonkovsky HL, Schrum LW (2011) microRNAs: fad or future of liver disease. World J Gastroenterol 17:2536–2542
Zhao WY, Wang DD, Song MQ, Yang L, Ye J, Chen LB (2011) Role of microRNA-223 and its target gene oncogene c-myc in hepatocellular carcinoma pathogenesis. Zhonghua Gan Zang Bing Za Zhi 19:114–117
Xu H, He JH, Xiao ZD, Zhang QQ, Chen YQ, Zhou H, Qu LH (2010) Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development. Hepatology 52:1431–1442
Girard M, Jacquemin E, Munnich A, Lyonnet S, Henrion-Caude A (2008) miR-122, a paradigm for the role of microRNAs in the liver. J Hepatol 48:648–656
Hou W, Tian Q, Zheng J, Bonkovsky HL (2010) MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins. Hepatology 51:1494–1504
Liu X, Wang T, Wakita T, Yang W (2010) Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology 398:57–67
Scagnolari C, Zingariello P, Vecchiet J, Selvaggi C, Racciatti D, Taliani G, Riva E, Pizzigallo E, Antonelli G (2010) Differential expression of interferon-induced microRNAs in patients with chronic hepatitis C virus infection treated with pegylated interferon alpha. Virol J 7:311
Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, Janssen J, Koppe C, Knolle P, Castoldi M, Tacke F, Trautwein C, Luedde T (2011) Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology 53:209–218
Kwiecinski MEN, Noetel A, Schievenbusch S, Strack I, Toex U, Drebber U, Steffen H, Dienes HP, Odenthal M (2010) miR-29, inhibiting synthesis of profibrogenic mediators, is released into the blood stream after chronic hepatitis C infection, indicating progression of fibrosis. Hepatology 52(4 Suppl):119A
Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G, Voros D (2013) Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog 52:297–303
Wong QW, Ching AK, Chan AW, Choy KW, To KF, Lai PB, Wong N (2010) MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling. Clin Cancer Res 16:867–875
Han ZB, Zhong L, Teng MJ, Fan JW, Tang HM, Wu JY, Chen HY, Wang ZW, Qiu GQ, Peng ZH (2012) Identification of recurrence-related microRNAs in hepatocellular carcinoma following liver transplantation. Mol Oncol 6:445–457
Chen L, Jiang M, Yuan W, Tang H (2012) miR-17-5p as a novel prognostic marker for hepatocellular carcinoma. J Invest Surg 25:156–161
Wang G, Kwan BC, Lai FM, Chow KM, Li PK, Szeto CC (2012) Urinary miR-21, miR-29, and miR-93: novel biomarkers of fibrosis. Am J Nephrol 36:412–418
Schwabe RF (2011) Wang TC (2011) Targeting liver cancer: first steps toward a miracle? Cancer Cell 20:698–699
Acknowledgments
All authors thank to Mersin University Scientific Research Fund for their financial support [Project no. BAP-SBE FM (ZÖ) 2011-5 YL].
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Oksuz, Z., Serin, M.S., Kaplan, E. et al. Serum microRNAs; miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive biomarkers for HCV-positive cirrhosis and hepatocellular carcinoma. Mol Biol Rep 42, 713–720 (2015). https://doi.org/10.1007/s11033-014-3819-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-014-3819-9