遗传 ›› 2015, Vol. 37 ›› Issue (6): 517-527.doi: 10.16288/j.yczz.14-443
孙凌云1, 2, 李星逾2, 孙志为2
收稿日期:2014-12-15
修回日期:2015-03-24
出版日期:2015-06-20
发布日期:2015-05-14
通讯作者:
孙志为,教授,研究方向：肝胆外科、微创外科、移植外科、消化道肿瘤。E-mail: 2833570686@qq.com
作者简介:孙凌云,硕士研究生,专业方向：分子靶向治疗肝细胞癌的临床及实验。E-mail: sly84@qq.com
基金资助:Lingyun Sun1, 2, Xingyu Li2, Zhiwei Sun2
Received:2014-12-15
Revised:2015-03-24
Online:2015-06-20
Published:2015-05-14
摘要： 肝癌是一种严重危害人类健康的恶性疾病,在全世界患癌人群中,肝癌的发生率排第五,死亡率排第二。原发性肝癌(Hepatocellular carcinoma, HCC)是最普遍的肝癌组织学亚型,属于异质性疾病,对其治疗涉及遗传学、基因组学、环境毒理学等多个领域。尽管许多分子靶向治疗药物如索拉菲尼等已经进入临床应用并证明有效,但细胞毒性等负效应不容忽视,目前迫切需要新的治疗靶点和药物高效并选择性的杀伤肝癌细胞。大量证据表明,肝脏肿瘤的发生和发展与表观遗传学密切相关,DNA甲基化、组蛋白修饰、miRNA表达的异常及表观遗传相关基因表达的异常都是HCC中显著的表观遗传异常现象。表观治疗药物可能会逆转异常基因的表达,从而使HCC的发生和发展得以控制。文章综述了HCC表观遗传学治疗方面的研究进展,展望了未来利用类似的疗法治疗肝癌的潜力。
孙凌云, 李星逾, 孙志为. 原发性肝癌的表观遗传学及其治疗[J]. 遗传, 2015, 37(6): 517-527.
Lingyun Sun, Xingyu Li, Zhiwei Sun. Progress of epigenetics and its therapeutic application in hepatocellular carcinoma[J]. HEREDITAS(Beijing), 2015, 37(6): 517-527.
| [1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin , 2011, 61(2): 69-90. [2] El-Serag HB. Hepatocellular carcinoma. N Engl J Med , 2011, 365(12): 1118-1127. [3] Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol , 2009, 27(9): 1485-1491. [4] El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology , 2007, 132(7): 2557-2576. [5] Gish RG. Hepatocellular carcinoma: overcoming challenges in disease management. Clin Gastroenterol Hepatol , 2006, 4(3): 252-261. [6] Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin , 2012, 62(6): 394-399. [7] Tsim NC, Frampton AE, Habib NA, Jiao LR. Surgical treatment for liver cancer. World J Gastroenterol , 2010, 16(8): 927-933. [8] Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med , 2008, 359(4): 378-390. [9] Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol , 2009, 10(1): 25-34. [10] Kelley RK, Nimeiri HS, Munster PN, Vergo MT, Huang Y, Li CM, Hwang J, Mulcahy MF, Yeh BM, Kuhn P, Luttgen MS, Grabowsky JA, Stucky-Marshall L, Korn WM, Ko AH, Bergsland EK, Benson AB, Venook AP. Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dose-finding trial with pharmacokinetic and biomarker correlates. Ann Oncol , 2013, 24(7): 1900-1907. [11] Chan SL, Yeo W. Targeted therapy of hepatocellular carcinoma: present and future. J Gastroenterol Hepatol , 2012, 27(5): 862-872. [12] Pogribny IP, Rusyn I. Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma. Cancer Lett , 2014, 342(2): 223-230. [13] Hlady RA, Tiedemann RL, Puszyk W, Zendejas I, Roberts LR, Choi JH, Liu C, Robertson KD. Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis. Oncotarget , 2014, 5(19): 9425-9443. [14] Gao XD, Qu JH, Chang XJ, Lu YY, Bai WL, Wang H, Xu ZX, An LJ, Wang CP, Zeng Z, Yang YP. Hypomethylation of long interspersed nuclear element-1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma. Liver Int , 2014, 34(1): 136-146. [15] Hinrichsen I, Kemp M, Peveling-Oberhag J, Passmann S, Plotz G, Zeuzem S, Brieger A. Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs. PLoS One , 2014, 9(1): e84453. [16] Herceg Z, Paliwal A. Epigenetic mechanisms in hepatocellular carcinoma: how environmental factors influence the epigenome. Mutat Res , 2011, 727(3): 55-61. [17] Hernandez-Vargas H, Lambert MP, Le Calvez-Kelm F, Gouysse G, McKay-Chopin S, Tavtigian SV, Scoazec JY, Herceg Z. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors. PLoS One , 2010, 5(3): e9749. [18] Song MA, Tiirikainen M, Kwee S, Okimoto G, Yu H, Wong LL. Elucidating the landscape of aberrant DNA methylation in hepatocellular carcinoma. PLoS One , 2013, 8(2): e55761. [19] Shen J, Wang S, Zhang YJ, Kappil M, Wu HC, Kibriya MG, Wang Q, Jasmine F, Ahsan H, Lee PH, Yu MW, Chen CJ, Santella RM. Genome-wide DNA methylation profiles in hepatocellular carcinoma. Hepatology , 2012, 55(6): 1799-1808. [20] He CC, Xu JY, Zhang JL, Xie D, Ye H, Xiao ZY, Cai MY, Xu K, Zeng YJ, Li HG, Wang J. High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum Pathol , 2012, 43(9): 1425-1435. [21] Cai MY, Hou JH, Rao HL, Luo RZ, Li M, Pei XQ, Lin MC, Guan XY, Kung HF, Zeng YX, Xie D. High expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients. Mol Med , 2011, 17(1-2): 12-20. [22] Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature , 2007, 449(7164): 919-922. [23] Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, Saïb A, Voinnet O. A cellular microRNA mediates antiviral defense in human cells. Science , 2005, 308(5721): 557-560. [24] Hu W, Wang XJ, Ding XR, Li Y, Zhang XJ, Xie PW, Yang J, Wang SQ. MicroRNA-141 represses HBV replication by targeting PPARA. PLoS One , 2012, 7(3): e34165. [25] 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. [26] Kutay H, Bai SM, Datta J, Motiwala T, Pogribny I, Frankel W, Jacob ST, Ghoshal K. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem , 2006, 99(3): 671-678. [27] Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene , 2006, 25(17): 2537-2545. [28] Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, Lin CD, Liao YL, Wang JL, Chau YP, Hsu MT, Hsiao M, Huang HD, Tsou AP. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology , 2009, 49(5): 1571-1582. [29] Xu XJ, Fan ZY, Kang L, Han JQ, Jiang CY, Zheng XF, Zhu ZM, Jiao HB, Lin J, Jiang K, Ding LH, Zhang H, Cheng L, Fu HJ, Song Y, Jiang Y, Liu JH, Wang RF, Du N, Ye QN. Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis. J Clin Invest , 2013, 123(2): 630-645. [30] Cheetham SW, Gruhl F, Mattick JS, Dinger ME. Long noncoding RNAs and the genetics of cancer. Br J Cancer , 2013, 108(12): 2419-2425. [31] Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discov , 2011, 1(5): 391-407. [32] Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA , 2009, 106(28): 11667-11672. [33] Redon S, Reichenbach P, Lingner J. The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res , 2010, 38(17): 5797-5806. [34] Saito Y, Hibino S, Saito H. Alterations of epigenetics and microRNA in hepatocellular carcinoma. Hepatol Res , 2014, 44(1): 31-42. [35] Panzitt K, Tschernatsch MMO, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck CR, Denk H, Schroeder R, Trauner M, Zatloukal K. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology , 2007, 132(1): 330-342. [36] Du YM, Kong GY, You XN, Zhang S, Zhang T, Gao YE, Ye LH, Zhang XD. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18. J Biol Chem , 2012, 287(31): 26302-26311. [37] Huang JF, Guo YJ, Zhao CX, Yuan SX, Wang Y, Tang GN, Zhou WP, Sun SH. Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-r egulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology , 2013, 57(5): 1882-1892. [38] Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, Wu LM, Chen LM, Zheng SS. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol , 2012, 29(3): 1810-1816. [39] Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, Zheng SS. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol , 2011, 18(5): 1243-1250. [40] Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, Yang Y, Wang RY, Yang S, Huo XS, Zhang L, Wang F, Sun SH, Zhou WP. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology , 2012, 56(6): 2231-2241. [41] Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, Shang JL, Gao CF, Zhang FR, Wang F, Sun SH. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology , 2011, 54(5): 1679-1689. [42] Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov , 2006, 5(1): 37-50. [43] Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol , 2009, 10(3): 223-232. [44] Issa JPJ, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2’- deoxycytidine (decitabine) in hematopoietic malignancies. Blood , 2004, 103(5): 1635-1640. [45] Issa JPJ, Gharibyan V, Cortes J, Jelinek J, Morris G, Verstovsek S, Talpaz M, Garcia-Manero G, Kantarjian HM. Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate. J Clin Oncol , 2005, 23(17): 3948-3956. [46] Tsai HC, Li HL, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA. Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell , 2012, 21(3): 430-446. [47] Nakamura K, Aizawa K, Nakabayashi K, Kato N, Yamauchi J, Hata K, Tanoue A. DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis. PLoS One , 2013, 8(1): e54036. [48] Andersen JB, Factor VM, Marquardt JU, Raggi C, Lee YH, Seo D, Conner EA, Thorgeirsson SS. An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer. Sci Transl Med , 2010, 2(54): 54ra77. [49] Tao SF, Zhang CS, Guo XL, Xu Y, Zhang SS, Song JR, Li R, Wu MC, Wei LX. Anti-tumor effect of 5-aza-2’-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells. World J Gastroenterol , 2012, 18(19): 2334-2343. [50] Siedlecki P, Zielenkiewicz P. Mammalian DNA methyltransferases. Acta Biochim Pol , 2006, 53(2): 245-256. [51] Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A, MacLeod AR. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet , 2002, 33(1): 61-65. [52] Stefanska B, Salame P, Bednarek A, Fabianowska-Majewska K. Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Brit J Nut , 2012, 107(6): 781-790. [53] Qin TC, Jelinek J, Si JL, Shu JM, Issa JP. Mechanisms of resistance to 5-aza-2’-deoxy-cytidine in human cancer cell lines. Blood , 2009, 113(3): 659-667. [54] Beumer JH, Eiseman JL, Parise RA, Joseph E, Holleran JL, Covey JM, Egorin MJ. Pharmacokinetics, metabolism, andoral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2’-deoxycytidine in mice. Clin Cancer Res , 2006, 12(24): 7483-7491. [55] Weber B, Kimhi S, Howard G, Eden A, Lyko F. Hypomethylation of a LINE-1 antisense promoter in the cMet locus impairs Met signalling through induction of illegitimate transcription. Oncogene , 2010, 29(43): 5775-5784. [56] Kantarjian H, Oki Y, Garcia-Manero G, Huang XL, O’Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan JQ, Davis J, Giles F, Saba HI, Issa JP. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood , 2007, 109(1): 52-57. [57] Shen Y, Takahashi M, Byun H, Link A, Sharma N, Balaguer F, Leung H, Boland C, Goel A. Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells. Cancer Biol Ther , 2012, 13(7): 542-552. [58] Foubister V. Drug reactivates genes to inhibit cancer. Drug Discov Today , 2003, 8(10): 430-431. [59] Carlisi D, Vassallo B, Lauricella M, Emanuele S, D’Anneo A, Di Leonardo E, Di Fazio P, Vento R, Tesoriere G. Histone deacetylase inhibitors induce in human hepatoma HepG2 cells acetylation of p53 and histones in correlation with apoptotic effects. Int J Oncol , 2008, 32(1): 177-184. [60] Carlisi D, Lauricella M, D’Anneo A, Emanuele S, Angileri L, Di Fazio P, Santulli A, Vento R, Tesoriere G. The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitises human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL-DISC activation. Eur J Cancer , 2009, 45(13): 2425-2438. [61] Ma BBY, Sung F, Tao Q, Poon FF, Lui VW, Yeo W, Chan SL, Chan ATC. The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines. Invest New Drugs , 2010, 28(2): 107-114. [62] Yeo W, Chung HC, Chan SL, Wang LZ, Lim R, Picus J, Boyer M, Mo FKF, Koh J, Rha SY, Hui EP, Jeung HC, Roh JK, Yu SC, To KF, Tao Q, Ma BB, Chan AWH, Tong JHM, Erlichman C, Chan ATC, Goh BC. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group. J Clin Oncol , 2012, 30(27): 3361-3367. [63] Zhang CZ, Pan YH, Cao Y, Lai PBS, Liu LL, Chen GG, Yun JP. Histone deacetylase inhibitors facilitate dihydroartemisinininduced apoptosis in liver cancer in vitro and in vivo. PLoS One , 2012, 7(6): e39870. [64] Lin KT, Wang YW, Chen CT, Ho CM, Su WH, Jou YS. HDAC inhibitors augmented cell migration and metastasis through induction of PKCs leading to identification of low toxicity modalities for combination cancer therapy. Clin Cancer Res , 2012, 18(17): 4691-4701. [65] Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Shep-pard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature , 2012, 488(7411): 404-408. [66] Raggi C, Factor VM, Seo D, Holczbauer A, Gillen MC, Marquardt JU, Andersen JB, Durkin M, Thorgeirsson SS. Epigenetic reprogramming modulates malignant properties of human liver cancer. Hepatology , 2014, 59(6): 2251-2262. [67] Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science , 2007, 317(5834): 121-124. [68] Park EJ, Lee JH, Yu GY, He GB, Ali SR, Holzer RG, Osterreicher CH, Takahashi H, Karin M. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell , 2010, 140(2): 197-208. [69] Gramantieri L, Fornari F, Callegari E, Sabbioni S, Lanza G, Croce CM, Bolondi L, Negrini M. MicroRNA involvement in hepatocellular carcinoma. J Cell Mol Med , 2008, 12(6A): 2189-2204. [70] Borel F, Konstantinova P, Jansen PLM. Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol , 2012, 56(6): 1371-1383. [71] Henry JC, Azevedo-Pouly ACP, Schmittgen TD. MicroRNA replacement therapy for cancer. Pharm Res , 2011, 28(12): 3030-3042. [72] Weiler J, Hunziker J, Hall J. Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther , 2006, 13(6): 496-502. [73] Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with ‘antagomirs’. Nature , 2005, 438(7068): 685-689. [74] Elmén J, Lindow M, Schütz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjärn M, Hansen HF, Berger U, Gullans S, Kearney P, Sarnow P, Straarup EM, Kauppinen S. LNA-mediated microRNA silencing in non-human primates. Nature , 2008, 452(7189): 896-899. [75] Ji JF, Shi J, Budhu A, Yu ZP, Forgues M, Roessler S, Ambs S, Chen YD, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med , 2009, 361(15): 1437-1447. [76] Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell , 2009, 137(6): 1005-1017. [77] Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides GA, Jaeger SA, Ogata H, Karin M, Struhl K, Hadzopoulou-Cladaras M, Iliopoulos D. An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell , 2011, 147(6): 1233-1247. [78] [78] Sánchez Y, Huarte M. Long non-coding RNAs: challenges for diagnosis and therapies. Nucleic Acid Ther , 2013, 23(1): 15-20. [79] Stefanska B, Karlic H, Varga F, Fabianowska-Majewska K, Haslberger AG. Epigenetic mechanisms in anti-cancer actions of bioactive food components—the implications in cancer prevention. Br J Pharmacol , 2012, 167(2): 279-297. [80] Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics , 2011, 3(4): 503-518. [81] Anestopoulos I, Voulgaridou GP, Georgakilas AG, Franco R, Pappa A, Panayiotidis MI. Epigenetic therapy as a novel approach in hepatocellular carcinoma. Pharmacol Ther , 2015, 145: 103-119. [82] Lachenmayer A, Toffanin S, Cabellos L, Alsinet C, HoshidaY, Villanueva A, Minguez B, Tsai HW, Ward SC, Thung S, Friedman SL, Llovet JM. Combination therapy for hepatocellular carcinoma: additive preclinical efficacy of the HDAC inhibitor panobinostat with sorafenib. J Hepatol , 2012, 56(6): 1343-1350. [83] Li GM, Wang YG, Pan Q, Wang J, Fan JG, Sun C. RNAi screening with shRNAs against histone methylation-related genes reveals determinants of sorafenib sensitivity in hepatocellular carcinoma cells. Int J Clin Exp Pathol , 2014, 7(3): 1085-1092. [84] Guo ZS, Hong JA, Irvine KR, Chen GA, Spiess PJ, Liu Y, Zeng G, Wunderlich JR, Nguyen DM, Restifo NP, Schrump DS. De novo induction of a cancer/testis antigen by 5-aza-2’ -deoxycytidine augments adoptive immunotherapy in a murine tumor model. Cancer Res , 2006, 66(2): 1105-1113. [85] Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Cron M, Fatho M, Lennerz V, Wölfel T, Hölzel M, Tüting T. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature , 2012, 490(7420): 412-416. [86] Coral S, Sigalotti L, Colizzi F, Spessotto A, Nardi G, Cortini E, Pezzani L, Fratta E, Fonsatti E, Di Giacomo AM, Nicotra MR, Natali PG, Altomonte M, Maio M. Phenotypic and functional changes of human melanoma xenografts induced by DNA hypomethylation: immunotherapeutic implications. J Cell Physiol , 2006, 207(1): 58-66. [87] Porta C, De Amici M, Quaglini S, Paglino C, Tagliani F, Boncimino A, Moratti R, Corazza GR. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann Oncol , 2008, 19(2): 353-358. [88] Ozen C, Yildiz G, Dagcan AT, Cevik D, Ors A, Keles U, Topel H, Ozturk M. Genetics and epigenetics of liver cancer. N Biotechnol , 2013, 30(4): 381-384. |
| [1] | 张競文,续倩,李国亮. 癌症发生发展中的表观遗传学研究[J]. 遗传, 2019, 41(7): 567-581. |
| [2] | 马志鹏, 陈军. 无义突变与“遗传补偿效应”[J]. 遗传, 2019, 41(5): 359-364. |
| [3] | 黄鑫,陈永强,徐国良,彭淑红. 脂肪组织DNA甲基化与糖尿病和肥胖的发生发展[J]. 遗传, 2019, 41(2): 98-110. |
| [4] | 饶琳, 孟飞龙, 房冉, 蔡晨依, 赵小立. MicroRNA调控耳蜗毛细胞发育的分子机制[J]. 遗传, 2019, 41(11): 994-1008. |
| [5] | 潘云枫, 王演怡, 陈静雯, 范怡梅. 线粒体代谢介导的表观遗传改变与衰老研究[J]. 遗传, 2019, 41(10): 893-904. |
| [6] | 夏蒙蒙,申雪沂,牛长敏,夏静,孙红亚,郑英. MicroRNA参与调控睾丸支持细胞的增殖与粘附功能[J]. 遗传, 2018, 40(9): 724-732. |
| [7] | 刘海龙, 谌阳, 高杨, 周玲, 韩晓松, 赵长志, 杨高娟, 陈毅龙, 杨慧, 谢胜松. 靶向miRNA前体不同类型sgRNA的丰度及特异性评估[J]. 遗传, 2018, 40(7): 561-571. |
| [8] | 鞠君毅,赵权. γ-珠蛋白基因表达调控机制与临床应用[J]. 遗传, 2018, 40(6): 429-444. |
| [9] | 肖娟, 王讯, 罗毅, 李晓开, 李学伟. 附睾小体功能蛋白及sRNA研究进展[J]. 遗传, 2018, 40(3): 197-206. |
| [10] | 施剑,李艳明,方向东. 长链非编码RNA通过细胞核高级结构调控真核基因表达及其临床意义[J]. 遗传, 2017, 39(3): 189-199. |
| [11] | 岳敏, 杨禹, 郭改丽, 秦曦明. 哺乳动物生物钟的遗传和表观遗传研究进展[J]. 遗传, 2017, 39(12): 1122-1137. |
| [12] | 秦辰雨, 蔡禾, 卿涵睿, 李利, 张红平. 长链非编码RNA H19对哺乳动物肌肉生长发育的调控[J]. 遗传, 2017, 39(12): 1150-1157. |
| [13] | 李新云, 付亮亮, 程会军, 赵书红. MicroRNA调控哺乳动物骨骼肌发育[J]. 遗传, 2017, 39(11): 1046-1053. |
| [14] | 刘辰东, 杨露, 蒲红州, 杨琼, 黄文耀, 赵雪, 朱砺, 张顺华. 运动对骨骼肌基因表达的表观遗传调控作用[J]. 遗传, 2017, 39(10): 888-896. |
| [15] | 魏俊,陆秀君,张晓林,梅梅,黄晓丽. MicroRNA在种子发育、休眠与萌发过程中的作用[J]. 遗传, 2017, 39(1): 14-21. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:
