Advances in targeted induction of DNA methylation and cancer therapy

Abstract

Abstract: DNA methylation is one of the important events in epigenetic regulation.It inhibits gene expression in the transcription level resulting in gene silencing.Recent studies revealed that DNA methylation not only occurs naturally in organism, but also targeting induced by special RNA DNA.Oncogenesis exist abnormally low methylation in tumor cells, which is considered to be one of the pathogeneses of tumors.Thus inhibition of the expression of oncogenesis and the growth of tumor by targeted induction of DNA methylation provides a new way for cancer therapy.This review summarizes the effects of targeted induction of DNA methylation on cancer therapy in preclinical studies.

Key words: DNA methylation, gene silencing, epigenetic regulation, cancer therapy

CLC Number:

R73-3

MA Ai-niu, WANG Yong-xiang, ZHOU Xiang-jun. Advances in targeted induction of DNA methylation and cancer therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(3): 241-244.

References

[1] Cheng X, Roberts RJ.AdoMet-dependent methylation, DNA methyltransferase and base flipping[J].NucleicAcids Res, 2001, 29(18):3784-3795.
[2] Jeltsch A.Beyond Watson and Crick:DNA methylation and molecular enzymology of DNA methy ltransferases[J]. Chembiochem, 2002, 3(4):274-293.
[3] Kanai Y, Ushijima S, Nakanishi Y, et al.Mutation of the DNA methy ltransferase (DNMT) 1 gene in human colorectal cancers[J].Cancer Lett, 2003, 192(1):75-82.
[4] Sardi I, Dal-Canto M, Bartoletti R, et al.Molecular genetic alterations of c-my c oncogene in superficial and locally advanced bladder cancer[J].Eur Urol, 1998, 33(4):424-430.
[5] Gupta A, Godwin AK, Vanderveer L, et al.Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression breast carcinoma and ovarian carcinoma[J].Cancer Res, 2003, 63(3):664-673.
[6] Jones PA.DNA methylation and cancer[J].Oncogene, 2002, 21(35):5358-5360.
[7] Gonzalez-Zulueta M, Bender CM, Yang AS, et al.Methylation of the 5'CpG island of the p16 CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing[J].Cancer Res, 1995, 55(20):4531-4535.
[8] Momparler RL.Epigenetic therapy of cancer with 5-aza-2'-deoxycytidine (decitabine)[J].Semin Oncol, 2005, 32(5):443-451.
[9] Murgo AJ.Innovative approaches to the clinical development of DNA methylation inhibitors as epigenetic remodeling drugs[J].Semin Oncol, 2005, 32(5):458-464.
[10] Laird PW, Jackson-Grusby L, Fazeli A, et al.Suppression of intestinal neoplasia by DNA hypomethylation[J]. Cell, 1995, 81(2):197-205.
[11] Wassenegger M, Heimes S, Riedel L, et al.RNA-directed de novo methylation of genomic sequences in plants[J]. Cell, 1994, 76(3):567-576.
[12] Sijen T, Vijn I, Rebocho A, et al.Transcriptional and posttranscriptional gene silencing are mechanistically related[J].Curr Biol, 2001, 11(6):436-440.
[13] Kawasaki H, Taira K.Induction of DNA methylation and gene silencing by short interfering RNAs in human cells[J].Nature, 2004, 431(7005):211-217.
[14] Morris KV, Chan SW, Jacobsen SE, et al.Small interfering RNA-induced transcriptional gene silencing in human cells[J].Science, 2004, 305(5688):1289-1292.
[15] Kawasaki H, Taira K, Morris KV.siRNA induced transcriptional gene silencing in mammalian cells[J].Cell Cycle, 2005, 4(3):442-448.
[16] Castanotto D, Tommasi S, Li M, et al.Short hairpin RNA-directed cytosine(CpG) methylation of the RASSF1A gene promoter in HeLa cells[J].Mol Ther, 2005, 2(1): 179-183.
[17] Yao XM, Hu JF, Dabueks M, et al.A methylated oligonucleotide inhibits IGF2 expression and enhances survival in a model of hepatocellular carcinoma[J].J Clin Invest, 2003, 111(2):265-273.
[18] Mita AC, Mita MM, Nawrocki ST, et al.survivin:key regulator of mitosis and apoptosis and novel target for cancer therapeutics[J].Clin Cancer Res, 2008, 14(16): 5000-5005.
[19] Warnecke PM, Stirzaker C, Song J, et al.Identification and resolution of artifacts in bisulfite sequencing[J]. Methods, 2002, 27(2):101-107.
[20] Wells J, Farnham PJ.Characterizing transcription factor binding sites using formaldehyde crosslinking and immuynoprecipition[J].Methods, 2002, 26(1):48-56.
[21] Lachner M, O'Sullivan RJ, Jenuwein T.An epigenetic road map for histone lysine methylation[J].J Cell Sci, 2003, 116(Pt 11):2117-2124.
[22] Quina AS, Buschbeck M, Di Croce L.Chromatin structure and epigenetics[J].Biochem Pharmacol, 2006, 72(11):1563-1569.