ISSN: 2375-3811
International Journal of Biological Sciences and Applications  
Manuscript Information
 
 
Correlation of miR-122 with Bcl-w is a Paradigm for the Role of Micro RNAs in the Liver Injury Development
International Journal of Biological Sciences and Applications
Vol.2 , No. 6, Publication Date: Dec. 11, 2015, Page: 86-96
1582 Views Since December 11, 2015, 986 Downloads Since Dec. 11, 2015
 
 
Authors
 
[1]    

Shaden Muawia, Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.

[2]    

Hala H. El-Said, Department of Clinical Biochemistry, National Liver Institute, Menofiya University, Shebin El Kom City, Egypt.

[3]    

Tarek M. Kamel, Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.

 
Abstract
 

Circulating miR-122 is commonly deregulated in liver fibrosis and hepatocellular carcinoma (HCC). In this study we tried to explore the potential usefulness of serum miR-122 as noninvasive diagnostic marker for liver injury and HCC in chronic hepatitis C virus infected patients. In addition, tried to examine whether serum level of miR-122 can potentially serve as circulating marker for liver disease stage assessment. Out of 84 participants; 20 patients were HCV positive infected patients, 44 HCC patients infected with HCV, and 20 healthy volunteers were also included. We determined the expression of levels ofmiR-122 and Bcl-w in serum using (qRT-PCR); and compared them with the other clinicopathological parameters. Mean miR-122 expression levels were up-regulated in both patient groups (HCV and HCC) compared to control group. In addition, mean expression levels of miR-122 were significantly higher in HCV group compared to HCC group (p=0.025). Conversely, mean Bcl-w expression levels were down-regulated in both patient groups compared to control group but, mean expression levels of Bcl-w were significantly higher in HCC group compared to HCV group(p=<0.001). Furthermore, expression levels of miR-122 were positively correlated with ALT, AST, ALP and fibrosis stage, and negatively correlated with prothrombin concentration and Albumin in both patient groups.ROC curve analysis for miR-122 yielded 64% sensitivity and 75% specificity for the differentiation of HCC patients from non-HCC at a cutoff 3.85. Conclusion: miR-122 can be used as novel biomarker for liver injury and may be used to discriminate patients with HCC from HCV. Also, miR-122 may represent novel non invasive biomarker for assessment of liver disease severity in patients with chronic hepatitis C virus.


Keywords
 

Micro RNA-122, Bcl-w, Chronic Hepatitis, Hepatocellular Carcinoma (HCC), Hepatitis C virus (HCV)


Reference
 
[01]    

Czepiel J, Biesiada G, Mach T. Viral hepatitis C; Pol Arch Med Wewn. (2008); 118(12): 734-40.

[02]    

Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology (2004); 127: S5-S16.

[03]    

El-Zayadi AR, Badran HM, Barakat EM, Attia Mel-D, Shawky S, Mohamed MK, Selim O, Saeid A. Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol (2005); 11: 5193-5198.

[04]    

Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology (2002); 122: 1609-19.

[05]    

Schuppan D, AfdhalNH. Liver cirrhosis. Lancet (2008); 371: 838–851.

[06]    

Bataller R, Brenner DA. Liver fibrosis. J Clin Invest (2005); 115: 209–218.

[07]    

Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology (2003); 38: 1449 1457.

[08]    

Nguyen-Khac E, Capron D. Noninvasive diagnosis of liver fibrosis by ultrasonic transient elastography (Fibroscan). Eur J Gastroenterol Hepatol (2006); 18: 1321–1325.

[09]    

Koch A, Horn A, Duckers H, Yagmur E, Sanson E, Bruensing J, et al. Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically illnon-cirrhotic patients at a medical ICU. Crit Care (2011); 15: R266.

[10]    

Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol, (2006); 13(12), 1097-101.

[11]    

Friedman RC, Farh KK, Burge CB, Bartel DP.. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. (2009); 9: 92–105.

[12]    

Garzon R, Calin GA, Croce CM.. MicroRNAs in Cancer. Annu Rev Med. (2009); 60: 167–79.

[13]    

Jopling, C. L., M. Yi, A. M. Lancaster, S. M. Lemon, and P. Sarnow. Modulation of hepatitis C virus RNA abundance by a liver-specific micro RNA. Science (2005); 309: 1577-1581.

[14]    

L. Gramantieri, M. Ferracin, F. Fornari, A. Veronese, S. Sabbioni, C.G. Liu, G.A.Calin, C. Giovannini, E. Ferrazzi, G.L. Grazi, C.M. Croce, L. Bolondi, M. Negrini, Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma, Cancer Res.(2007); 67: 6092–6099.

[15]    

A. Krek, D. Grun, M.N. Poy, R. Wolf, L. Rosenberg, E.J. Epstein, P. Mac Menamin,I. da Piedade, K.C. Gunsalus, M. Stoffel, N. Rajewsky, Combinatorial microRNA target predictions, Nat. Genet. (2005); 37: 495–500.

[16]    

L. Gibson, S.P. Holmgreen, D.C. Huang, O. Bernard, N.G. Copeland, N.A. Jenkins, G.R. Sutherland, E. Baker, J.M. Adams, S. Cory, bcl-w, a novel member of thebcl-2 family, promotes cell survival, Oncogene(1996);13: 665–675.

[17]    

Paynord T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOS VIRC groups. Lancet (1997); 349: 82532.

[18]    

Morishima C, Morgan TR, Everhart JE, et al. HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial. Hepatol, (2006); 44: 360–7.

[19]    

Sato Y, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. New Engl J Med, (1993); 328, 25: 1802-1806.

[20]    

Chen, C., Ridzon, D.A., Broomer, A.J., Zhou, Z., Lee, D.H., Nguyen, J.T., Barbisin, M., Xu, N.L., Mahuvakar, V.R., Andersen, M.R., Lao, K.Q., Livak, K.J. and Guegler, K.J. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res, (2005); 33(20) e179.

[21]    

Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C (T) method. Nat Protoc, (2008); 3: 1101–1108.

[22]    

Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.T., Mullis, K.B. and Erlich, H.A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science (1988); 239: 487–491.

[23]    

Hilden J., Glaziou P., Regret graphs-diagnostic uncertainty and Youden index, Statistics in medicine (1996);15: 969-86.

[24]    

Chang M, Marquardt AP, Wood BL, et al. In situ distribution of hepatitis C virus replicative-intermediate RNA in hepatic tissue and its correlation with liver disease. J Virol. (2000); 74: 944–955.

[25]    

Davila J A, Morgan RO, and Shaiby Y. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population–based study. Gastroenterology (2004); 127: 1372-1376.

[26]    

Kashyap R, Join A, Nalesnik M, Carr B, Barnes J, Vargas HE, et al.. Clinical significance of elevated alpha-fetoprotein in adults and children. Dig Dis Sci.(2001); 46: 1709–13.

[27]    

Yang S Z, Dong J H, Li K et al. Detection of AFP mRNA and MAGE1-mRNA as markers of disseminated hepatocellular carcinoma cells in blood Hepatobiliary Pancreatic Dis Int, (2005); 4 (2): 227–233.

[28]    

Scholz A, Rehm VA, Rieke S et al. Angiopoietin -2 serum levels are elevated in patients with liver cirrhosis and hepatocellular carcinoma. Am J Gastroentrol (2007); 102: 2471- 2481.

[29]    

Tangkijvanich P, Anukulkamkusol N, Suwangool P, Lert-maharit S, Hanvivatvong O, Kullavanijaya P, et al.. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol (2000); 31: 302–8.

[30]    

Frank C. Circulating tumor cells measurements in hepatocellular carcinoma.. Int J Hepatol http (2012);//dx.doi.org/10.1155/2012/68480.

[31]    

Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res.(2009); 9: 92–105.

[32]    

Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene (2006); 25: 2537–2545.

[33]    

Ura S, Honda M, Yamashita T et al. Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology (2009); 49: 1098–1112.

[34]    

Chang J, Guo JT, Jiang D, Guo H, Taylor JM et al. Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells J. Virol (2008); 82(16): 8215–8223.

[35]    

Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, et al Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev(2009); 23(11): 1313–1326.

[36]    

Shan Y, Zheng J, Lambrecht RW, Bonkovsky HL. Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology (2007); 133: 1166–1174.

[37]    

Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med (2013); 368: 1685–1694. doi: 10.1056/nejmoa1209026.

[38]    

Poynard T, Mathurin P, Lai CL, Guyader D, Poupon R, Tainturier MH, et al. A comparison of fibrosis progression in chronic liver diseases. J Hepatol (2003); 38: 257–265.

[39]    

Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology (2003); 38: 1449–1457.

[40]    

Koch A, Horn A, Duckers H, Yagmur E, Sanson E, Bruensing J, et al. Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically ill non-cirrhotic patients at a medical ICU. Crit Care (2011); 15: R266.

[41]    

Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L. Circulating MicroRNAs in Patients with Chronic Hepatitis C and Non-Alcoholic Fatty Liver Disease. PLoS ONE (2011); (8):e23937.doi:10.1371/journal.pone.

[42]    

Trebicka J, Anadol E, Elfimova N, Strack I, Roggendorf M, Viazov S, Wedemeyer I, Drebber U, Rockstroh J, Sauerbruch T, Dienes HP, Odenthal M. Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis. J Hepatol (2013); 58: 234-239.

[43]    

Bihrer V, Friedrich-Rust M, Kronenberger B, Forestier N, Haupenthal J, et al.. Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol (2011); 106(9): 1663-9.

[44]    

Varnholt H, Drebber U, Schulze F, Wedemeyer I, Schirmacher P, Dienes HP, Odenthal M. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology (2008); 47(4): 1223-32.

[45]    

Zhang Y, Jia Y, Zheng R, Guo Y, Wang Y, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chemo(2010); 56: 1830–1838.

[46]    

Xu J, Wu C, Che X, Wang L, Yu D, et al. Circulating microRNAs, miR- 21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog (2011); 50: 136–142.

[47]    

Köberle V, Kronenberger B, Pleli T. Trojan J et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma European Journal of Cancer (2013); 49(16): 3442-3449.

[48]    

Ezzat H, Lotfy AM, Alalfy MN, El-Taher SM, Mokhtar A, Mohamed SA, El-Senosy FM. The Significance of Circulating Micro RNA-122 as a Non Invasive Diagnostic Marker of liver injury in Egyptian Chronic Hepatitis C virus Infected and Cirrhotic Patients with and without Hepatocellular Carcinoma. Clinical Medicine and Diagnostics (2014); 4 (1): 1-8.

[49]    

J. S.McDonald, D. Milosevic, H. V. Reddi, S. K. Grebe, and A. A. Schimnich. “Analysis of circulating microRNA: preanalytical and analytical challenges,” Clinical Chemistry (2011); 57: 833–840.

[50]    

Lin CJ,Gong H Y, Tseng H C, Wang W L, Wu J L. MiR-122 targets an apoptotic gene, Bcl-w in human hepatocellular carcinoma cell lines. Biochem. And Biophys. Research communication(2008); 375: 315-320.

[51]    

Kumar S, Chawla YK, Ghosh S, Chakraborti A. Over expression of MicroRNA -122 (MIR-122) induces apoptosis by targeting cyclin G1 and Bcl-w genes in vitro.20th annual conference of INASL (2012); 29: 140-148.

[52]    

Wang K, Zhang S, Weber J, Baxter D, Galas DJ Export of microRNAs and microRNA-protective protein by mammalian cells. Nucl Acids Res (2010); 38: 7248–7259.





 
  Join Us
 
  Join as Reviewer
 
  Join Editorial Board
 
share:
 
 
Submission
 
 
Membership