Role of microRNAs in hepatocellular carcinoma: A clinical perspective

OncoTargets and Therapy

Volumn 6, Issue , 2013, Pages 1167-1178

  Callegari, Elisa ^a   Elamin, Bahaeldin K ^a,b   Sabbioni, Silvia ^a   Gramantieri, Laura ^c   Negrini, Massimo ^a  

^a UNIVERSITY OF FERRARA   (Italy)

^b UNIVERSITY OF KHARTOUM   (Sudan)

^c UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Hepatocellular carcinoma; Micromarkers; microRNA; Oncolytic viruses

Indexed keywords

ANTAGOMIR; BETA CATENIN; LONTUCIREV; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; MICRORNA; MICRORNA 122; MICRORNA 126; MICRORNA 141; MICRORNA 199; MICRORNA 200C; MICRORNA 21; MICRORNA 221; MIRAVIRSEN; ONCOLYTIC VIRUS; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN P53; TALIMOGENE LAHERPAREPVEC; UNCLASSIFIED DRUG; WNT PROTEIN;

3' UNTRANSLATED REGION; ANTINEOPLASTIC ACTIVITY; CANCER CLASSIFICATION; CANCER PROGNOSIS; CELL CYCLE ARREST; DOWN REGULATION; DRUG EFFICACY; DRUG SAFETY; EPIGENETICS; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENETIC ASSOCIATION; HUMAN; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; NONHUMAN; REVIEW; TRANSCRIPTION REGULATION; TUMOR SUPPRESSOR GENE; UPREGULATION;

EID: 84979256697     PISSN: None     EISSN: 11786930     Source Type: Journal    
DOI: 10.2147/OTT.S36161     Document Type: Review

References (160)

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74-108.
2. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893-1907.
3. Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 2005;9(2):191-211.
4. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6(9):674-687.
5. Purohit V, Rapaka R, Kwon OS, Song BJ. Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma. Life Sci. 2013;92(1):3-9.
6. Wu HC, Santella R. The role of aflatoxins in hepatocellular carcinoma. Hepat Mon. 2012;12(10 HCC):e7238.
7. Uccello M, Malaguarnera G, Corriere T, Biondi A, Basile F, Malaguarnera M. Risk of hepatocellular carcinoma in workers exposed to chemicals. Hepat Mon. 2012;12(10 HCC):e5943.
8. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51(5):1820-1832.
9. Dragani TA. Risk of HCC: genetic heterogeneity and complex genetics. J Hepatol. 2010;52(2):252-257.
10. Shrimal A, Prasanth M, Kulkarni AV. Interventional radiological treatment of hepatocellular carcinoma: an update. Indian J Surg. 2012;74(1): 91-99.
11. Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006;24(26):4293-4300.
12. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-390.
13. Kane RC, Farrell AT, Madabushi R, et al. Sorafenib for the treatment of unresectable hepatocellular carcinoma. Oncologist. 2009;14(1): 95-100.
14. Kostner AH, Sorensen M, Olesen RK, Gronbaek H, Lassen U, Ladekarl M. Sorafenib in advanced hepatocellular carcinoma: a nationwide retrospective study of efficacy and tolerability. Scientific World Journal. 2013;2013:931972.
15. Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 2010;26(3): 189-195.
16. Bai W, Wang YJ, Zhao Y, et al. Sorafenib in combination with transarterial chemoembolization improves survival of unresectable hepatocellular carcinoma: a propensity-score matching study. J Dig Dis. 2013;14(4):181-190.
17. Zhao Y, Wang WJ, Guan S, et al. Sorafenib combined with transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma: a large-scale multicenter study of 222 patients. Ann Oncol. March 18, 2013;24(7):1786-92.
18. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297.
19. Griffiths-Jones S. miRBase: microRNA sequences and annotation. Curr Protoc Bioinformatics. 2010;Chapter 12:Unit 12.9.1-10.
20. Davis-Dusenbery BN, Hata A. Mechanisms of control of microRNA biogenesis. J Biochem. 2010;148(4):381-392.
21. Farazi TA, Hoell JI, Morozov P, Tuschl T. MicroRNAs in human cancer. Adv Exp Med Biol. 2013;774:1-20.
22. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857-866.
23. Negrini M, Ferracin M, Sabbioni S, Croce CM. MicroRNAs in human cancer: from research to therapy. J Cell Sci. 2007;120(Pt 11): 1833-1840.
24. Costinean S, Zanesi N, Pekarsky Y, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A. 2006;103(18):7024-7029.
25. Santanam U, Zanesi N, Efanov A, et al. Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A. 2010;107(27):12210-12215.
26. Enomoto Y, Kitaura J, Hatakeyama K, et al. Emu/miR-125b transgenic mice develop lethal B-cell malignancies. Leukemia. 2011;25(12): 1849-1856.
27. Zhao JL, Rao DS, Boldin MP, Taganov KD, O’Connell RM, Baltimore D. NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci U S A. 2011;108(22):9184-9189.
28. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature. 2010;467(7311):86-90.
29. Klein U, Lia M, Crespo M, et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell. 2010;17(1):28-40.
30. Negrini M, Gramantieri L, Sabbioni S, Croce CM. microRNA involvement in hepatocellular carcinoma. Anticancer Agents Med Chem. 2011;11(6):500-521.
31. Hou J, Lin L, Zhou W, et al. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 2011;19(2):232-243.
32. 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):735-739.
33. Xu H, He JH, Xiao ZD, et al. Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development. Hepatology. 2010;52(4):1431-1442.
34. Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2): 87-98.
35. Krutzfeldt J, Stoffel M. MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab. 2006;4(1):9-12.
36. Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284(46):32015-32027.
37. Ma L, Liu J, Shen J, et al. Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells. Cancer Biol Ther. 2010;9(7):554-561.
38. Fornari F, Gramantieri L, Giovannini C, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009;69(14):5761-5767.
39. Tsai WC, Hsu PW, Lai TC, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571-1582.
40. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28(40):3526-3536.
41. Hsu SH, Wang B, Kota J, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Invest. 2012;122(8):2871-2883.
42. Tsai WC, Hsu SD, Hsu CS, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest. 2012;122(8):2884-2897.
43. Gramantieri L, Ferracin M, Fornari F, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67(13):6092-6099.
44. Jensen MR, Factor VM, Fantozzi A, Helin K, Huh CG, Thorgeirsson SS. Reduced hepatic tumor incidence in cyclin G1-deficient mice. Hepatology. 2003;37(4):862-870.
45. Lin CJ, Gong HY, Tseng HC, Wang WL, Wu JL. miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2008;375(3):315-320.
46. Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25(17):2537-2545.
47. Jiang J, Gusev Y, Aderca I, et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res. 2008;14(2):419-427.
48. Jia XQ, Cheng HQ, Qian X, et al. Lentivirus-mediated overexpression of microRNA-199a inhibits cell proliferation of human hepatocellular carcinoma. Cell Biochem Biophys. 2012;62(1):237-244.
49. Fornari F, Milazzo M, Chieco P, et al. MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2010;70(12):5184-5193.
50. Kim S, Lee UJ, Kim MN, et al. MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem. 2008;283(26):18158-18166.
51. Wang C, Song B, Song W, et al. Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1alpha in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients. J Gastroenterol Hepatol. 2011;26(11):1630-1637.
52. Henry JC, Park JK, Jiang J, et al. miR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2010;403(1):120-125.
53. Shen Q, Cicinnati VR, Zhang X, et al. Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer. 2010;9:227.
54. Fornari F, Gramantieri L, Ferracin M, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene. 2008;27(43):5651-5661.
55. Medina R, Zaidi SK, Liu CG, et al. MicroRNAs 221 and 222 bypass quiescence and compromise cell survival. Cancer Res. 2008;68(8):2773-2780.
56. Garofalo M, Di Leva G, Romano G, et al. miR-221 and 222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16(6):498-509.
57. Pineau P, Volinia S, McJunkin K, et al. miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci U S A. 2010;107(1): 264-269.
58. Callegari E, Elamin BK, Giannone F, et al. Liver tumorigenicity promoted by microRNA-221 in a mouse transgenic model. Hepatology. 2012;56(3):1025-1033.
59. Gramantieri L, Fornari F, Ferracin M, et al. MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clin Cancer Res. 2009;15(16):5073-5081.
60. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257-2261.
61. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65(14): 6029-6033.
62. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene. 2007;26(19):2799-2803.
63. Buscaglia LE, Li Y. Apoptosis and the target genes of microRNA-21. Chin J Cancer. 2011;30(6):371-380.
64. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647-658.
65. 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(15):2128-2236.
66. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2008;283(2):1026-1033.
67. Ferracin M, Veronese A, Negrini M. Micromarkers: miRNAs in cancer diagnosis and prognosis. Expert Rev Mol Diagn. 2010;10(3): 297-308.
68. Minguez B, Lachenmayer A. Diagnostic and prognostic molecular markers in hepatocellular carcinoma. Dis Markers. 2011;31(3):181-190.
69. Barshack I, Meiri E, Rosenwald S, et al. Differential diagnosis of hepatocellular carcinoma from metastatic tumors in the liver using microRNA expression. Int J Biochem Cell Biol. 2010;42(8):1355-1362.
70. Hess KR, Varadhachary GR, Taylor SH, et al. Metastatic patterns in adenocarcinoma. Cancer. 2006;106(7):1624-1633.
71. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther. 2009;9(6):703-711.
72. Qi J, Wang J, Katayama H, Sen S, Liu SM. Circulating microRNAs (cmiRNAs) as novel potential biomarkers for hepatocellular carcinoma. Neoplasma. November 12, 2013;60(2):135-42.
73. 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(2):136-142.
74. 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;6(8):e23937.
75. Tomimaru Y, Eguchi H, Nagano H, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56(1): 167-175.
76. Trebicka J, Anadol E, Elfimova N, et al. Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis. J Hepatol. 2013;58(2):234-239.
77. van der Meer AJ, Farid WR, Sonneveld MJ, et al. Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122. J Viral Hepat. 2013;20(3): 158-166.
78. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005;438(7068):685-689.
79. Elmen J, Lindow M, Schutz S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452(7189):896-899.
80. Mercatelli N, Coppola V, Bonci D, et al. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice. PLoS One. 2008;3(12):e4029.
81. Felicetti F, Errico MC, Bottero L, et al. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res. 2008;68(8): 2745-2754.
82. Di Martino MT, Gulla A, Cantafio ME, et al. In vitro and in vivo anti-tumor activity of miR-221/222 inhibitors in multiple myeloma. Oncotarget. 2013;4(2):242-255.
83. Park JK, Kogure T, Nuovo GJ, et al. miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res. 2011;71(24): 7608-7616.
84. Leone E, Morelli E, Di Martino MT, et al. Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth. Clin Cancer Res. 2013;19(8):2096-2106.
85. Lindow M, Kauppinen S. Discovering the first microRNA-targeted drug. J Cell Biol. 2012;199(3):407-412.
86. Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327(5962):198-201.
87. Hildebrandt-Eriksen ES, Aarup V, Persson R, Hansen HF, Munk ME, Orum H. A locked nucleic acid oligonucleotide targeting microRNA 122 is well-tolerated in cynomolgus monkeys. Nucleic Acid Ther. 2012;22(3):152-161.
88. Kota J, Chivukula RR, O’Donnell KA, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137(6):1005-1017.
89. He XX, Chang Y, Meng FY, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31(28):3357-3369.
90. Xiong Y, Fang JH, Yun JP, et al. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010;51(3):836-845.
91. Akao Y, Nakagawa Y, Hirata I, et al. Role of anti-oncomirs miR-143 and-145 in human colorectal tumors. Cancer Gene Ther. 2010;17(6): 398-408.
92. Kitade Y, Akao Y. MicroRNAs and their therapeutic potential for human diseases: microRNAs, miR-143 and-145, function as anti-oncomirs and the application of chemically modified miR-143 as an anti-cancer drug. J Pharmacol Sci. 2010;114(3):276-280.
93. Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A. MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res. 2011;71(15): 5214-5224.
94. Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA. Activation of miR-31 function in already-established metastases elicits metastatic regression. Genes Dev. 2011;25(6):646-659.
95. Bader AG. miR-34-a microRNA replacement therapy is headed to the clinic. Front Genet. 2012;3:120.
96. Kasinski AL, Slack FJ. miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma. Cancer Res. 2012;72(21): 5576-5587.
97. Di Martino MT, Leone E, Amodio N, et al. Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence. Clin Cancer Res. 2012;18(22):6260-6270.
98. Lou W, Chen Q, Ma L, et al. Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model. J Mol Med (Berl). 2013;91(6):715-725.
99. Bischoff JR, Kirn DH, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996;274(5286):373-376.
100. Mathis JM, Stoff-Khalili MA, Curiel DT. Oncolytic adenoviruses-selective retargeting to tumor cells. Oncogene. 2005;24(52):7775-7791.
101. Alemany R. Cancer selective adenoviruses. Mol Aspects Med. 2007;28(1):42-58.
102. Ganly I, Kirn D, Eckhardt G, et al. A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res. 2000;6(3):798-806.
103. Nemunaitis J, Ganly I, Khuri F, et al. Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. Cancer Res. 2000;60(22):6359-6366.
104. Galanis E, Okuno SH, Nascimento AG, et al. Phase I-II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas. Gene Ther. 2005;12(5):437-445.
105. Opyrchal M, Aderca I, Galanis E. Phase I clinical trial of locoregional administration of the oncolytic adenovirus ONYX-015 in combination with mitomycin-C, doxorubicin, and cisplatin chemotherapy in patients with advanced sarcomas. Methods Mol Biol. 2009;542:705-717.
106. Khuri FR, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med. 2000;6(8):879-885.
107. Nemunaitis J, Swisher SG, Timmons T, et al. Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. J Clin Oncol. 2000;18(3):609-622.
108. Patel MR, Kratzke RA. Oncolytic virus therapy for cancer: the first wave of translational clinical trials. Transl Res. 2013;161(4):355-364.
109. Hu JC, Coffin RS, Davis CJ, et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 2006;12(22):6737-6747.
110. Harrington KJ, Hingorani M, Tanay MA, et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16(15):4005-4015.
111. Cerullo V, Pesonen S, Diaconu I, et al. Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients. Cancer Res. 2010;70(11):4297-4309.
112. Pesonen S, Diaconu I, Cerullo V, et al. Integrin targeted oncolytic adenoviruses Ad5-D24-RGD and Ad5-RGD-D24-GMCSF for treatment of patients with advanced chemotherapy refractory solid tumors. Int J Cancer. 2012;130(8):1937-1947.
113. Kanerva A, Nokisalmi P, Diaconu I, et al. Anti-viral and anti-tumor T-cell immunity in patients treated with GMCSF coding oncolytic adenovirus. Clin Cancer Res. 2013;19(10):2734-2744.
114. Park BH, Hwang T, Liu TC, et al. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 2008;9(6):533-542.
115. Hwang TH, Moon A, Burke J, et al. A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma. Mol Ther. 2011;19(10):1913
116. Heo J, Reid T, Ruo L, et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med. 2013;19(3):329-336.
117. Kelly EJ, Hadac EM, Greiner S, Russell SJ. Engineering microRNA responsiveness to decrease virus pathogenicity. Nat Med. 2008;14(11): 1278-1283.
118. Ylosmaki E, Hakkarainen T, Hemminki A, Visakorpi T, Andino R, Saksela K. Generation of a conditionally replicating adenovirus based on targeted destruction of E1A mRNA by a cell type-specific MicroRNA. J Virol. 2008;82(22):11009-11015.
119. Ylosmaki E, Lavilla-Alonso S, Jaamaa S, et al. MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver. PLoS One. 2013;8(1):e54506.
120. Cawood R, Chen HH, Carroll F, Bazan-Peregrino M, van Rooijen N, Seymour LW. Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells. PLoS Pathog. 2009;5(5):e1000440.
121. Cawood R, Wong SL, Di Y, Baban DF, Seymour LW. MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity. PLoS One. 2011;6(1):e16152.
122. Leja J, Nilsson B, Yu D, et al. Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability. PLoS One. 2010;5(1):e8916.
123. Jin H, Lv S, Yang J, et al. Use of microRNA Let-7 to control the replication specificity of oncolytic adenovirus in hepatocellular carcinoma cells. PLoS One. 2011;6(7):e21307.
124. Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12(2):133-143.
125. Suh MR, Lee Y, Kim JY, et al. Human embryonic stem cells express a unique set of microRNAs. Dev Biol. 2004;270(2):488-498.
126. Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435(7044):974-978.
127. Ma S. Biology and clinical implications of CD133(+) liver cancer stem cells. Exp Cell Res. 2013;319(2):126-132.
128. Oishi N, Wang XW. Novel therapeutic strategies for targeting liver cancer stem cells. Int J Biol Sci. 2011;7(5):517-535.
129. Lee TK, Cheung VC, Ng IO. Liver tumor-initiating cells as a therapeutic target for hepatocellular carcinoma. Cancer Lett. 2012. May 8, 2013. [Epub ahead of print.]
130. Pang RW, Poon RT. Cancer stem cell as a potential therapeutic target in hepatocellular carcinoma. Curr Cancer Drug Targets. 2012;12(9): 1081-1094.
131. Budhu A, Jia HL, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology. 2008;47(3): 897-907.
132. Han ZB, Zhong L, Teng MJ, et al. Identification of recurrence-related microRNAs in hepatocellular carcinoma following liver transplantation. Mol Oncol. 2012;6(4):445-457.
133. Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361(15):1437-1447.
134. Viswanathan SR, Powers JT, Einhorn W, et al. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 2009;41(7):843-848.
135. Zhang Y, Guo X, Xiong L, et al. MicroRNA-101 suppresses SOX9-dependent tumorigenicity and promotes favorable prognosis of human hepatocellular carcinoma. FEBS Lett. 2012;586(24):4362-4370.
136. Li W, Xie L, He X, et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer. 2008;123(7):1616-1622.
137. Gu H, Guo X, Zou L, Zhu H, Zhang J. Upregulation of microRNA-372 associates with tumor progression and prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;375(1-2):23-30.
138. Fu X, Wang Q, Chen J, et al. Clinical significance of miR-221 and its inverse correlation with p27 Kip(1) in hepatocellular carcinoma. Mol Biol Rep. 2011;38(5):3029-3035.
139. Rong M, Chen G, Dang Y. Increased miR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro. BMC Cancer. 2013;13:21.
140. Chen L, Jiang M, Yuan W, Tang H. miR-17-5p as a novel prognostic marker for hepatocellular carcinoma. J Invest Surg. 2012;25(3): 156-161.
141. Han ZB, Chen HY, Fan JW, Wu JY, Tang HM, Peng ZH. Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation. J Cancer Res Clin Oncol. 2012;138(1):153-161.
142. Chen HY, Han ZB, Fan JW, et al. miR-203 expression predicts outcome after liver transplantation for hepatocellular carcinoma in cirrhotic liver. Med Oncol. 2012;29(3):1859-1865.
143. Murakami Y, Tamori A, Itami S, et al. The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis. BMC Cancer. 2013;13:99.
144. Xu J, Zhu X, Wu L, et al. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/beta-catenin pathway. Liver Int. 2012;32(5):752-760.
145. Qi P, Cheng SQ, Wang H, Li N, Chen YF, Gao CF. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One. 2011;6(12):e28486.
146. Li J, Wang Y, Yu W, Chen J, Luo J. Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. Biochem Biophys Res Commun. 2011;406(1):70-73.
147. Gui J, Tian Y, Wen X, et al. Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci (Lond). 2011;120(5):183-193.
148. Liu AM, Yao TJ, Wang W, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2(2):e000825.
149. Shrivastava S, Petrone J, Steele R, Lauer GM, Bisceglie AM, Ray RB. Upregulation of circulating miR-20a is correlated with hepatitis C virus mediated liver disease progression. Hepatology. February 6, 2013. [Epub ahead of print.]
150. Ji J, Yamashita T, Budhu A, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;50(2):472-480.
151. Ji J, Yamashita T, Wang XW. Wnt/beta-catenin signaling activates microRNA-181 expression in hepatocellular carcinoma. Cell Biosci. 2011;1(1):4.
152. Xu C, Liu S, Fu H, et al. MicroRNA-193b regulates proliferation, migration and invasion in human hepatocellular carcinoma cells. Eur J Cancer. 2010;46(15):2828-2836.
153. Ma S, Tang KH, Chan YP, et al. miR-130b promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 2010;7(6):694-707.
154. Jung CJ, Iyengar S, Blahnik KR, et al. Epigenetic modulation of miR-122 facilitates human embryonic stem cell self-renewal and hepatocellular carcinoma proliferation. PLoS One. 2011;6(11):e27740.
155. Jia Y, Liu H, Zhuang Q, et al. Tumorigenicity of cancer stem-like cells derived from hepatocarcinoma is regulated by microRNA-145. Oncol Rep. 2012;27(6):1865-1872.
156. Zhang J, Luo N, Luo Y, Peng Z, Zhang T, Li S. microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb. Int J Oncol. 2012;40(3): 747-756.
157. Oishi N, Kumar MR, Roessler S, et al. Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma. Hepatology. 2012;56(5):1792-1803.
158. Wu K, Ding J, Chen C, et al. Hepatic transforming growth factor beta gives rise to tumor-initiating cells and promotes liver cancer development. Hepatology. 2012;56(6):2255-2267.
159. Xia H, Ooi LL, Hui KM. MiR-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology. March 7, 2013. [Epub ahead of print.]
160. Xia H, Ooi LL, Hui KM. MiR-214 targets beta-catenin pathway to suppress invasion, stem-like traits and recurrence of human hepatocellular carcinoma. PLoS One. 2012;7(9):e44206.