Transcriptional regulation and therapy of hTERT in hepatocellular carcinoma
-
摘要: 细胞增殖失控和凋亡障碍是肝细胞癌(HCC)发生、发展的重要机制和关键过程。人端粒酶逆转录酶(hTERT)与细胞的生理性和病理性增生密切相关,hTERTmRNA的表达受到多种癌基因、抑癌基因以及细胞因子的调控,与HCC的发生、发展等相关。近年来以hTERT为靶点的基因疗法如RNA干扰、反义技术和自杀基因技术等成为HCC辅助治疗的新策略。本文就hTERT转录水平的激活与HCC发生、发展、预后的关系,以及靶向hTERT基因治疗HCC的研究进展作一综述。Abstract: Unlimited cell proliferation and disabled apoptosis are the most important event and crucial step in the occurrence and development of hepatocellular carcinoma (HCC) .Human telomerase reverse transcriptase (hTERT) and physiological and pathological cell proliferation are closely related, and its transcriptional level is regulated by numerous oncogenes, anti-oncogenes and cytokines.hTERT is related to the occurrence and development of hepatocellular carcinoma.Recently, hTERT-targeted gene therapy has become a novel strategy for the management of HCC.The relationships between the expression of hTERT and the tumor occurrence, progression, prognosis, as well as gene-targeted therapy on the sequence of hTERT for HCC are discussed in this review.
-
Key words:
- telomerase /
- carcinoma
-
[1]Li NF, Kocher HM, Salako MA, et al.A novel function ofcolony stimulating factor 1 receptor in hTERT immortalizationof human epithelialcells[J].Oncogene, 2009, 28 (5) :773-780. [2]Cassar L, Nicholls C, Pinto AR, et al.Bone morphogeneticprotein 7 induces telomerase inhibition, telomerase shorten-ing, breast cancer cell senescence, and death via smad3[J].FASEB J, 2009, 23 (6) :1880-1892. [3]Choi J, Min N, Park J, et al.TSA-induced DNMT1 downregulation represses Htert expression viarecruiting CTCF intodemethylated core promoter region of hTERT in HCT116[J].Biochem Biophys Res Commun, 2010, 391 (1) :449-454. [4]Verdel A, Vavasseur A, Le Gorrec M, et al.Common themes insiRNA-mediated epigenetic silencing pathways[J].Int J DevBiol, 2009, 53:245-257. [5]Horikawa I, Barrett JC.Cis-Activation of the human telom-erase gene (hTERT) by the hepatitis B virus genome[J].JNatl Caneer Inst, 2001, 93 (15) :1171-1173. [6]Hua L, Wei S, Fang L, et al.Hepatitis B virus X protein up-regulates transcriptional activation of human telomerase re-verse transcriptase[J].Virus Genes, 2010, 40:174-182. [7]Hua Liu, Fang Luan, Ying Ju, et al.In vitro transfection ofthe hepatitis B virus PreS2 gene into the human hepatocarci-nomacellline HepG2 induces upregulation of human telomer-ase reverse transcriptase[J].Biochem Biophys Res Com-mun, 2007, 355 (2) :379-384. [8]Straat K, Liu C, Rahbar A, et al.Activation of telomerase byhuman cytomegalovirus[J].J Natl Cancer Inst, 2009, 101 (7) :488-497. [9]VermaSC, Borah S, Robertson ES.Latency-associated nu-clear antigen of kaposi sarcoma-associated herpesvirus up-regulates transcription of human telomerase reverse tran-scriptase promoter through interaction with transcription fac-tor SP1[J].J virol, 2004, 78 (19) :1641-1645. [10]Zimmermann H, Degenkolbe R, Bernard HU, et al.Down-regulate p53 activity by targeting the transcriptional coactiva-tor CBP/p300[J].Virology, 1999, 73 (8) :6209-6219. [11]Wang J, Xie LY, Allan S, et al.Myc activates telomerase[J].Genes Dev.1998, 12:1769-1774. [12]Stephen T, Oh S, LaimonisaL.Telomerase activation by hu-man papillomavirus type 16 E6 protein:induction of humantelomerase reverse treanscriptase expression through Mycand GC-rich Spl binding sites[J].Virology, 2001, 75 (12) :5559-5566. [13]陈颖, 孔庆忠.端粒酶逆转录酶和P53在大鼠肝癌发生中的动态变化[J].世界华人消化杂志, 2009, 17 (15) :1493-1497. [14]Dong J, Wang L, Tian YP, et al.hTERT single nucleotidepolymorphism is associated with increased risks of hepato-cellular carcinomaand tumor metastasis[J].Nan Fang Yi KeDa Xue Xue Bao, 2011, 31 (1) :49-52. [15]Kong SY, Park JW, Kim JO, et al.Alpha-fetoprotein andhuman telomerase reverse transcriptase mRNA levels in pe-ripheral blood of patients with hepatocellular carcinoma[J].JCancer Res Clin Oncol, 2009, 135 (8) :1091-1098. [16]Daskalow K, Pfander D, Weichert W, et al.Distinct tempo-rospatial expression patterns of glycolysis-related proteins inhuman hepatocellular carcinoma[J].Histochem Cell Biol, 2009, 132:21-31. [17]Li H, Wang XL, Yang Y, et al.Inhibitory effect of RNAi tar-geting human telomerase reverse transcriptase against hu-man hepatocellular carcinoma cells[J].Nan Fang Yi Ke DaXue Xue Bao, 2008, 28 (8) :1323-1326. [18]Guo X, Wang W, Zhou F, et al.siRNA-mediated inhibitionof hTERT enhances chemosensitivity of hepatocellular carci-noma[J].Cancer Biol Ther, 2008, 7 (10) , 1555-1560. [19]Kamradt MC, Lu M, Werner ME, et al.The small heat shockprotein alphaB-crystallin is anovel inhibitor of TRAIL-inducedapoptosis that suppresses the activation of caspase-3[J].JBiol Chem, 2005, 280:11059-11066. [20]Zhang RG, Zhao JJ, Yang LQ, et al.RNA interference-me-diated hTERT inhibition enhances TRAIL-induced apoptosisin resistant hepatocellular carcinoma cells[J].Oncol Rep, 2010, 23 (4) :1013-1019. [21]Hu Y, Shen Y, Ji B, et al.Combinational RNAi gene therapyof hepatocellular carcinoma by targeting human EGFR andTERT[J].Eur J Pharm Sci, 2011, 42 (4) :387-391. [22]Miura N, Sato R, Tsukamoto T, et al.A noncoding RNAgene on chromosome 10p15.3 may function upstream ofhTERT[J].BMC Mol Biol, 2009, 10:5. [23]Su XL, Wen SS, Ying LC, et al.Antisense oligonucleotidetargeting at the initiator of hTERT arrests growth of hepatomacells[J].World J Gastroenterol, 2004, 10 (3) :366-370. [24]Lin RX, Tuo CW, L櫣QJ, et al.Inhibition of tumor growthand metastasis with antisense oligonucleotides (Cantide) tar-geting hTERT in an in situ human hepatocellular carcinomamodel[J].Acta Pharmacol Sin, 2005, 26 (6) :762-768. [25]Yang Y, Lv QJ, Du QY, et al.Combined effects of Cantideand chemotherapeutic drugs on inhibition of tumor cells’growth in vitro and in vivo[J].World J Gastroenterol.2005, 28, 11 (16) :2491-2496. [26]Song MS, Jeong JS, Ban G, et al.Validation of tissue-specific promoter-driven tumor-targeting trans-splicingribozyme system as a multifunctional cancer gene therapydevice in vivo[J].Cancer Gene Ther, 2009, 16 (2) :113-125. [27]Song J, Kim C, Ochoa ER.Sleeping Beauty-mediated sui-cide gene therapy of hepatocellular carcinoma[J].BiosciBiotechnol Biochem, 2009, 73 (1) :165-168. [28]刘燕, 邓志华, 杨长青, 等.重组腺病毒Ad-hTERTp-HSV-TK载体的构建及抗肝癌实验研究[J].肿瘤研究与临床, 2009, 2l (1) :4-6. [29]刘燕, 邓志华, 杨长青, 等.重组腺病毒Ad-hTERTp-HSV-TK/GCV系统的构建及其对人肝癌细胞HepG2的杀伤作用及旁观者效应研究[J].中国癌症杂志, 2009, 19 (1) :29-32.
本文二维码
计量
- 文章访问数: 3519
- HTML全文浏览量: 21
- PDF下载量: 712
- 被引次数: 0