Genome-Wide Analysis of DNA Methylation and Expression of MicroRNAs in Breast Cancer Cells

被引:33
作者
Morita, Sumiyo [1 ]
Takahashi, Ryou-u [2 ]
Yamashita, Riu [3 ]
Toyoda, Atsushi [4 ]
Horii, Takuro [1 ]
Kimura, Mika [1 ]
Fujiyama, Asao [4 ]
Nakai, Kenta [5 ]
Tajima, Shoji [6 ]
Matoba, Ryo [7 ]
Ochiya, Takahiro [2 ]
Hatada, Izuho [1 ]
机构
[1] Gunma Univ, Inst Mol & Cellular Regulat, Lab Genome Sci, Biosignal Genome Resource Ctr, Gunma 3718512, Japan
[2] Natl Canc Ctr, Div Mol & Cellular Med, Chuo Ku, Tokyo 1040045, Japan
[3] Tohoku Univ, Med Megabank Org, Dept Integrat Genom, Aoba Ku, Sendai, Miyagi 9808579, Japan
[4] Natl Inst Genet, Ctr Genet Resource Informat, Shizuoka 4118540, Japan
[5] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Minato Ku, Tokyo 1088639, Japan
[6] Osaka Univ, Inst Prot Res, Lab Epigenet, Suita, Osaka 5650871, Japan
[7] DNA Chip Res Inc, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
关键词
DNA methylation; microRNA; cancer; RNA-POLYMERASE III; PROMOTER HYPERMETHYLATION; DOWN-REGULATION; SCANNING METHOD; GENE; CHROMATIN; TRANSCRIPTION; ASSOCIATION; ISLANDS; FAMILY;
D O I
10.3390/ijms13078259
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
DNA methylation of promoters is linked to transcriptional silencing of protein-coding genes, and its alteration plays important roles in cancer formation. For example, hypermethylation of tumor suppressor genes has been seen in some cancers. Alteration of methylation in the promoters of microRNAs (miRNAs) has also been linked to transcriptional changes in cancers; however, no systematic studies of methylation and transcription of miRNAs have been reported. In the present study, to clarify the relation between DNA methylation and transcription of miRNAs, next-generation sequencing and microarrays were used to analyze the methylation and expression of miRNAs, protein-coding genes, other non-coding RNAs (ncRNAs), and pseudogenes in the human breast cancer cell lines MCF7 and the adriamycin (ADR) resistant cell line MCF7/ADR. DNA methylation in the proximal promoter of miRNAs is tightly linked to transcriptional silencing, as it is with protein-coding genes. In protein-coding genes, highly expressed genes have CpG-rich proximal promoters whereas weakly expressed genes do not. This is only rarely observed in other gene categories, including miRNAs. The present study highlights the epigenetic similarities and differences between miRNA and protein-coding genes.
引用
收藏
页码:8259 / 8272
页数:14
相关论文
共 29 条
[1]   The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer [J].
Ai, Lingbao ;
Kim, Wan-Ju ;
Demircan, Berna ;
Dyer, Lisa M. ;
Bray, Kevin J. ;
Skehan, Ryan R. ;
Massoll, Nicole A. ;
Brown, Kevin D. .
CARCINOGENESIS, 2008, 29 (03) :510-518
[2]   Methylation-induced repression - Belts, braces, and chromatin [J].
Bird, AP ;
Wolffe, AP .
CELL, 1999, 99 (05) :451-454
[3]   CPG-RICH ISLANDS AND THE FUNCTION OF DNA METHYLATION [J].
BIRD, AP .
NATURE, 1986, 321 (6067) :209-213
[4]   DNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing [J].
Brenet, Fabienne ;
Moh, Michelle ;
Funk, Patricia ;
Feierstein, Erika ;
Viale, Agnes J. ;
Socci, Nicholas D. ;
Scandura, Joseph M. .
PLOS ONE, 2011, 6 (01)
[5]   MDR1 promoter hypermethylation in MCF7 human breast cancer cells - Changes in chromatin structure induced by treatment with 5-aza-cytidine [J].
David, GL ;
Yegnasubramanian, S ;
Kumar, A ;
Marchi, VL ;
De Marzo, AM ;
Lin, XH ;
Nelson, WG .
CANCER BIOLOGY & THERAPY, 2004, 3 (06) :540-548
[6]  
FAIRCHILD CR, 1987, CANCER RES, V47, P5141
[7]   Timeline - The history of cancer epigenetics [J].
Feinberg, AP ;
Tycko, B .
NATURE REVIEWS CANCER, 2004, 4 (02) :143-153
[8]  
GRAFF JR, 1995, CANCER RES, V55, P5195
[9]   The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J].
Gregory, Philip A. ;
Bert, Andrew G. ;
Paterson, Emily L. ;
Barry, Simon C. ;
Tsykin, Anna ;
Farshid, Gelareh ;
Vadas, Mathew A. ;
Khew-Goodall, Yeesim ;
Goodall, Gregory J. .
NATURE CELL BIOLOGY, 2008, 10 (05) :593-601
[10]  
HATADA I, 1993, NUCLEIC ACIDS RES, V21, P5577, DOI 10.1093/nar/21.24.5577