The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Epigenetic Silencing of MicroRNA-34b/c and B-Cell Translocation Gene 4 Is Associated with CpG Island Methylation in Colorectal Cancer
Abstract
Altered expression of microRNA (miRNA) is strongly implicated in cancer, and recent studies have shown that, in cancer, expression of some miRNAs cells is silenced in association with CpG island hypermethylation. To identify epigenetically silenced miRNAs in colorectal cancer (CRC), we screened for miRNAs induced in CRC cells by 5-aza-2′-deoxycytidine (DAC) treatment or DNA methyltransferase knockout. We found that miRNA-34b (miR-34b) and miR-34c, two components of the p53 network, are epigenetically silenced in CRC; that this down-regulation of miR-34b/c is associated with hypermethylation of the neighboring CpG island; and that DAC treatment rapidly restores miR-34b/c expression. Methylation of the miR-34b/c CpG island was frequently observed in CRC cell lines (nine of nine, 100%) and in primary CRC tumors (101 of 111, 90%), but not in normal colonic mucosa. Transfection of precursor miR-34b or miR-34c into CRC cells induced dramatic changes in the gene expression profile, and there was significant overlap between the genes down-regulated by miR-34b/c and those down-regulated by DAC. We also found that the miR-34b/c CpG island is a bidirectional promoter which drives expression of both miR-34b/c and B-cell translocation gene 4 (BTG4); that methylation of the CpG island is also associated with transcriptional silencing of BTG4; and that ectopic expression of BTG4 suppresses colony formation by CRC cells. Our results suggest that miR-34b/c and BTG4 are novel tumor suppressors in CRC and that the miR-34b/c CpG island, which bidirectionally regulates miR-34b/c and BTG4, is a frequent target of epigenetic silencing in CRC. [Cancer Res 2008;68(11):4123–32]
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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RAS Is Regulated by the let-7 MicroRNA Family
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miR-15 and miR-16 induce apoptosis by targeting BCL2
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Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
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Cited by
A decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871
Sharma, S., Kelly, T. K., & Jones, P. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp220 · Cited by 2,637
MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review
Iorio, M. V., & Croce, C. M. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100209 · Cited by 1,739
The miR-34 family in cancer and apoptosis
Hermeking, H. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.56 · Cited by 1,236
Cancer epigenetics reaches mainstream oncology
Rodríguez-Paredes, M., & Esteller, M. (2011) · Nature Medicine · doi:10.1038/nm.2305 · Cited by 1,205
Metadata
- Authors
- Toyota, M., Suzuki, H., Sasaki, Y., Maruyama, R., Imai, K., Shinomura, Y., & Tokino, T.
- Venue
- Cancer Research
- Published
- 2008-06-01
- Volume
- 68
- Issue
- 11
- Pages
- 4123-4132
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2154294588
- Cited by
- 600
- References
- 44
- FWCI
- 19.36
- Type
- journal article
- Language
- en
- Open access
- closed
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- Toyota, M., Suzuki, H., Sasaki, Y., Maruyama, R., Imai, K., Shinomura, Y., & Tokino, T. (2008). Epigenetic Silencing of MicroRNA-34b/c and B-Cell Translocation Gene 4 Is Associated with CpG Island Methylation in Colorectal Cancer. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-0325
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