Skip to main content
Top
Published in: Tumor Biology 7/2016

01-07-2016 | Original Article

Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer

Authors: Tarek M. K. Motawi, Nermin A. H. Sadik, Olfat G. Shaker, Maggy H. Ghaleb

Published in: Tumor Biology | Issue 7/2016

Login to get access

Abstract

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. Because of their size, specificity, and relative stability in plasma, miRNAs can be used as diagnostic and prognostic biomarkers to monitor liver injury, such as that caused by hepatitis C virus (HCV) and liver cancer. In this study, we investigated miRNA expression patterns from the serum of Egyptian patients with HCV and liver cancer compared with matched healthy controls. Using microarray-based expression profiling followed by real-time quantitative polymerase chain reaction validation, we compared the levels of circulating miRNA-122 and miRNA-222 in serum from patients with hepatitis C virus (n = 40) and liver cancer (n = 60) to matched healthy controls (n = 30). MiRNA SNORD68 was the housekeeping endogenous control. We found that the serum levels of miR-122 and miR-222 were significantly elevated in HCV patients, but not in liver cancer patients, compared with controls. Receiver operating characteristic analysis revealed that miR-122 and miR-222 have a high diagnostic potential in discriminating patients with HCV from controls. Serum miR-222 was significantly higher in HCV patients compared to liver cancer patients. Our results indicate that serum miR-122 and miR-222 are elevated in Egyptian patients with chronic HCV, and these miRNAs have a strong potential to serve as novel biomarkers for liver injury but not specifically for liver cancer.
Literature
1.
go back to reference Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol. 1998;28(6):930–8.CrossRefPubMed Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol. 1998;28(6):930–8.CrossRefPubMed
2.
go back to reference Deuffic-Burban S, Mohamed MK, Larouze B, Carrat F, Valleron AJ. Expected increase in hepatitis C-related mortality in Egypt due to pre-2000 infections. J Hepatol. 2006;44(3):455–61.CrossRefPubMed Deuffic-Burban S, Mohamed MK, Larouze B, Carrat F, Valleron AJ. Expected increase in hepatitis C-related mortality in Egypt due to pre-2000 infections. J Hepatol. 2006;44(3):455–61.CrossRefPubMed
3.
go back to reference Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin Gastroenterol Hepatol. 2005;3 Suppl 2:S97–101.CrossRefPubMed Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin Gastroenterol Hepatol. 2005;3 Suppl 2:S97–101.CrossRefPubMed
5.
go back to reference Abdel-Aziz F, Habib M, Mohamed MK, Abdel-Hamid M, Gamil F, Madkour S, et al. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology. 2000;32:111–5.CrossRefPubMed Abdel-Aziz F, Habib M, Mohamed MK, Abdel-Hamid M, Gamil F, Madkour S, et al. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology. 2000;32:111–5.CrossRefPubMed
6.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMed Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMed
7.
go back to reference Kudo M. Hepatocellular carcinoma in 2011 and beyond: from the pathogenesis to molecular targeted therapy. Oncology. 2011;81 Suppl 1:1–10.CrossRefPubMed Kudo M. Hepatocellular carcinoma in 2011 and beyond: from the pathogenesis to molecular targeted therapy. Oncology. 2011;81 Suppl 1:1–10.CrossRefPubMed
8.
go back to reference Meguro M, Mizuguchi T, Kawamoto M, Hirata K .The molecular pathogenesis and clinical implications of hepatocellular carcinoma.Int J Hepatol. 2011; 818672.doi: 10.4061/2011/818672. Meguro M, Mizuguchi T, Kawamoto M, Hirata K .The molecular pathogenesis and clinical implications of hepatocellular carcinoma.Int J Hepatol. 2011; 818672.doi: 10.​4061/​2011/​818672.
9.
go back to reference Yamazaki K, Masugi Y, Sakamoto M. Molecular pathogenesis of hepatocellular carcinoma: altering transforming growth factor-beta signaling in hepatocarcinogenesis. Dig Dis. 2011;29(3):284–8. doi:10.1159/000327560.CrossRefPubMed Yamazaki K, Masugi Y, Sakamoto M. Molecular pathogenesis of hepatocellular carcinoma: altering transforming growth factor-beta signaling in hepatocarcinogenesis. Dig Dis. 2011;29(3):284–8. doi:10.​1159/​000327560.CrossRefPubMed
10.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2011;94(2):153–6.CrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2011;94(2):153–6.CrossRef
11.
go back to reference Yu MC, Yuan JM, Govindarajan S, Ross RK. Epidemiology of hepatocellular carcinoma. Can J Gastroenterol. 2000;14(8):703–9.CrossRefPubMed Yu MC, Yuan JM, Govindarajan S, Ross RK. Epidemiology of hepatocellular carcinoma. Can J Gastroenterol. 2000;14(8):703–9.CrossRefPubMed
13.
go back to reference Freedman LS, Edwards BK, Ries LAG, Young JL (eds.). Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER. 2006; NIH Pub. No. 06–5873. Bethesda: National Cancer Institute Freedman LS, Edwards BK, Ries LAG, Young JL (eds.). Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER. 2006; NIH Pub. No. 06–5873. Bethesda: National Cancer Institute
15.
go back to reference Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science. 2004;305(5689):1437–41.CrossRefPubMed Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science. 2004;305(5689):1437–41.CrossRefPubMed
17.
go back to reference Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMed Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMed
18.
go back to reference Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11(4):441–50.CrossRefPubMed Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11(4):441–50.CrossRefPubMed
20.
go back to reference Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.CrossRefPubMed Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.CrossRefPubMed
24.
go back to reference Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571–82. doi:10.1002/hep.22806.CrossRefPubMed Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571–82. doi:10.​1002/​hep.​22806.CrossRefPubMed
26.
go back to reference Le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. Embo J. 2007;26:3699–708.CrossRefPubMedPubMedCentral Le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. Embo J. 2007;26:3699–708.CrossRefPubMedPubMedCentral
27.
go back to reference Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, et al. MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 2012;61(11):1600–9.CrossRefPubMed Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, et al. MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 2012;61(11):1600–9.CrossRefPubMed
28.
go back to reference Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with “antagomirs”. Nature. 2005;438(7068):685–9.CrossRefPubMed Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with “antagomirs”. Nature. 2005;438(7068):685–9.CrossRefPubMed
29.
go back to reference Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem. 2006;99(3):671–8.CrossRefPubMedPubMedCentral Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem. 2006;99(3):671–8.CrossRefPubMedPubMedCentral
30.
go back to reference Xu Y, Xia F, Ma L, Shan J, Shen J, Yang Z, et al. MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest. Cancer Lett. 2011;310(3):160–9. doi:10.1016/j.canlet.2011.06.027.PubMed Xu Y, Xia F, Ma L, Shan J, Shen J, Yang Z, et al. MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest. Cancer Lett. 2011;310(3):160–9. doi:10.​1016/​j.​canlet.​2011.​06.​027.PubMed
31.
go back to reference Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85.PubMed Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85.PubMed
32.
33.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (−delta delta C (T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (−delta delta C (T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
36.
go back to reference Kanda T, Ishibashi O, Kawahigashi Y, Mishima T, Kosuge T, Mizuguchi Y, et al. Identification of obstructive jaundice-related microRNAs in mouse liver. Hepatogastroenterology. 2010;57(102–103):1013–23.PubMed Kanda T, Ishibashi O, Kawahigashi Y, Mishima T, Kosuge T, Mizuguchi Y, et al. Identification of obstructive jaundice-related microRNAs in mouse liver. Hepatogastroenterology. 2010;57(102–103):1013–23.PubMed
37.
go back to reference Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, et al. Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology. 2011;53:209–18. doi:10.1002/hep.23922.CrossRefPubMed Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, et al. Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology. 2011;53:209–18. doi:10.​1002/​hep.​23922.CrossRefPubMed
38.
go back to reference Huang J, Wang Y, Guo Y, Sun S. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 2010;52:60–70. doi:10.1002/hep.23660.CrossRefPubMed Huang J, Wang Y, Guo Y, Sun S. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 2010;52:60–70. doi:10.​1002/​hep.​23660.CrossRefPubMed
43.
go back to reference Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.CrossRefPubMed Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.CrossRefPubMed
44.
go back to reference Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science. 2005;309(5740):1577–81.CrossRefPubMed Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science. 2005;309(5740):1577–81.CrossRefPubMed
46.
go back to reference Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136–42. doi:10.1002/mc.20712.CrossRefPubMed Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136–42. doi:10.​1002/​mc.​20712.CrossRefPubMed
50.
go back to reference Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12(9):735–9.CrossRefPubMed Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12(9):735–9.CrossRefPubMed
51.
go back to reference Chang J, Nicolas E, Marks D, Sander C, Lerro A, Bnendra MA, et al. Mir-122, a mammalian liver-specific microRNA, is processed from her mRNA and may down regulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 2004;1(2):106–13.CrossRefPubMed Chang J, Nicolas E, Marks D, Sander C, Lerro A, Bnendra MA, et al. Mir-122, a mammalian liver-specific microRNA, is processed from her mRNA and may down regulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 2004;1(2):106–13.CrossRefPubMed
53.
go back to reference Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2):87–98.CrossRefPubMed Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2):87–98.CrossRefPubMed
58.
go back to reference Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest. 1995;96(5):2461–8.CrossRefPubMedPubMedCentral Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest. 1995;96(5):2461–8.CrossRefPubMedPubMedCentral
59.
go back to reference Rippe RA, Schrum LW, Stefanovic B, Solís-Herruzo JA, Brenner DA. NF-kappaB inhibits expression of the alpha 1(I) collagen gene. DNA Cell Biol. 1999;18(10):751–61.CrossRefPubMed Rippe RA, Schrum LW, Stefanovic B, Solís-Herruzo JA, Brenner DA. NF-kappaB inhibits expression of the alpha 1(I) collagen gene. DNA Cell Biol. 1999;18(10):751–61.CrossRefPubMed
60.
go back to reference Lang A, Schoonhoven R, Tuvia S, Brenner DA, Rippe RA. Nuclear factor kappaB in proliferation, activation and apoptosis in rat hepatic stellate cells. J Hepatol. 2000;33:49–58.CrossRefPubMed Lang A, Schoonhoven R, Tuvia S, Brenner DA, Rippe RA. Nuclear factor kappaB in proliferation, activation and apoptosis in rat hepatic stellate cells. J Hepatol. 2000;33:49–58.CrossRefPubMed
61.
go back to reference Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000;275(4):2247–50.CrossRefPubMed Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000;275(4):2247–50.CrossRefPubMed
63.
go back to reference Mazzocca A, Carloni V, Sciammetta S, Cordella C, Pantaleo P, Caldini A, et al. Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration. J Hepatol. 2002;37(3):322–30.CrossRefPubMed Mazzocca A, Carloni V, Sciammetta S, Cordella C, Pantaleo P, Caldini A, et al. Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration. J Hepatol. 2002;37(3):322–30.CrossRefPubMed
64.
go back to reference Cormier EG, Tsamis F, Kajumo F, Durso RJ, Gardner JP, Dragic T. CD81 is an entry coreceptor for hepatitis C virus. Proc Natl Acad Sci U S A. 2004;101(19):7270–4.CrossRefPubMedPubMedCentral Cormier EG, Tsamis F, Kajumo F, Durso RJ, Gardner JP, Dragic T. CD81 is an entry coreceptor for hepatitis C virus. Proc Natl Acad Sci U S A. 2004;101(19):7270–4.CrossRefPubMedPubMedCentral
65.
go back to reference Mazzocca A, Sciammetta SC, Carloni V, Cosmi L, Annunziato F, Harada T, et al. Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J Biol Chem. 2005;280(12):11329–39.CrossRefPubMed Mazzocca A, Sciammetta SC, Carloni V, Cosmi L, Annunziato F, Harada T, et al. Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J Biol Chem. 2005;280(12):11329–39.CrossRefPubMed
66.
go back to reference Bataller R, Paik YH, Lindquist JN, Lemasters JJ, Brenner DA. Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells. Gastroenterology. 2004;126(2):529–40.CrossRefPubMed Bataller R, Paik YH, Lindquist JN, Lemasters JJ, Brenner DA. Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells. Gastroenterology. 2004;126(2):529–40.CrossRefPubMed
67.
go back to reference Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67(13):6092–9.CrossRefPubMed Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67(13):6092–9.CrossRefPubMed
68.
go back to reference Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferracin M, Sabbioni S, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009;69(14):5761–7. doi:10.1158/0008-5472.CAN-08-4797.CrossRefPubMed Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferracin M, Sabbioni S, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009;69(14):5761–7. doi:10.​1158/​0008-5472.​CAN-08-4797.CrossRefPubMed
71.
go back to reference Fuse M, Kojima S, Enokida H, Chiyomaru T, Yoshino H, Nohata N, et al. Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on miRNA expression signature in prostate cancer. J Hum Genet. 2012;57(11):691–9. doi:10.1038/jhg.2012.95.CrossRefPubMed Fuse M, Kojima S, Enokida H, Chiyomaru T, Yoshino H, Nohata N, et al. Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on miRNA expression signature in prostate cancer. J Hum Genet. 2012;57(11):691–9. doi:10.​1038/​jhg.​2012.​95.CrossRefPubMed
74.
go back to reference Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11(11):1305–14. doi:10.1038/ncb1975.CrossRefPubMed Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11(11):1305–14. doi:10.​1038/​ncb1975.CrossRefPubMed
75.
go back to reference Reed SI. Control of the G1/S transition. Cancer Surv. 1997;29:7–23.PubMed Reed SI. Control of the G1/S transition. Cancer Surv. 1997;29:7–23.PubMed
76.
go back to reference Tsutsui T, Hesabi B, Moons DS, Pandolfi PP, Hansel KS, Koff A, et al. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27 (Kip1) activity. Mol Cell Biol. 1999;19(10):7011–9.CrossRefPubMedPubMedCentral Tsutsui T, Hesabi B, Moons DS, Pandolfi PP, Hansel KS, Koff A, et al. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27 (Kip1) activity. Mol Cell Biol. 1999;19(10):7011–9.CrossRefPubMedPubMedCentral
78.
go back to reference Li L, Rao JN, Guo X, Liu L, Santora R, Bass BL, et al. Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation. Am J Physiol Cell Physiol. 2001;281(3):C941–53.PubMed Li L, Rao JN, Guo X, Liu L, Santora R, Bass BL, et al. Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation. Am J Physiol Cell Physiol. 2001;281(3):C941–53.PubMed
79.
go back to reference Zou T, Mazan-Mamczarz K, Rao JN, Liu L, Marasa BS, Zhang AH, et al. Polyamine depletion increases cytoplasmic levels of RNA-binding protein HuR leading to stabilization of nucleophosmin and p53 mRNAs. J Biol Chem. 2006;281(28):19387–94.CrossRefPubMed Zou T, Mazan-Mamczarz K, Rao JN, Liu L, Marasa BS, Zhang AH, et al. Polyamine depletion increases cytoplasmic levels of RNA-binding protein HuR leading to stabilization of nucleophosmin and p53 mRNAs. J Biol Chem. 2006;281(28):19387–94.CrossRefPubMed
Metadata
Title
Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer
Authors
Tarek M. K. Motawi
Nermin A. H. Sadik
Olfat G. Shaker
Maggy H. Ghaleb
Publication date
01-07-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4884-6

Other articles of this Issue 7/2016

Tumor Biology 7/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine