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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2010-8-16
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pubmed:abstractText |
Global downregulation of microRNAs (miRNA) is a common feature in colorectal cancer (CRC). Whereas CpG island hypermethylation constitutes a mechanism for miRNA silencing, this field largely remains unexplored. Herein, we describe the epigenetic regulation of miR-137 and its contribution to colorectal carcinogenesis. We determined the methylation status of miR-137 CpG island in a panel of six CRC cell lines and 409 colorectal tissues [21 normal colonic mucosa from healthy individuals (N-N), 160 primary CRC tissues and their corresponding normal mucosa (N-C), and 68 adenomas]. TaqMan reverse transcription-PCR and in situ hybridization were used to analyze miR-137 expression. In vitro functional analysis of miR-137 was performed. Gene targets of miR-137 were identified using a combination of bioinformatic and transcriptomic approaches. We experimentally validated the miRNA:mRNA interactions. Methylation of the miR-137 CpG island was a cancer-specific event and was frequently observed in CRC cell lines (100%), adenomas (82.3%), and CRC (81.4%), but not in N-C (14.4%; P < 0.0001 for CRC) and N-N (4.7%; P < 0.0001 for CRC). Expression of miR-137 was restricted to the colonocytes in normal mucosa and inversely correlated with the level of methylation. Transfection of miR-137 precursor in CRC cells significantly inhibited cell proliferation. Gene expression profiling after miR-137 transfection discovered novel potential mRNA targets. We validated the interaction between miR-137 and LSD-1. Our data indicate that miR-137 acts as a tumor suppressor in the colon and is frequently silenced by promoter hypermethylation. Methylation silencing of miR-137 in colorectal adenomas suggests it to be an early event, which has prognostic and therapeutic implications.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-15620353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-15685193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-15944708,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-16079795,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-18403610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-18519671,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-18676867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-18996891,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20682795-19934284
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:copyrightInfo |
(c)2010 AACR.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6609-18
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:20682795-Aged,
pubmed-meshheading:20682795-Cell Growth Processes,
pubmed-meshheading:20682795-Cell Line, Tumor,
pubmed-meshheading:20682795-Cell Transformation, Neoplastic,
pubmed-meshheading:20682795-Colorectal Neoplasms,
pubmed-meshheading:20682795-Down-Regulation,
pubmed-meshheading:20682795-Epigenesis, Genetic,
pubmed-meshheading:20682795-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20682795-Gene Silencing,
pubmed-meshheading:20682795-HCT116 Cells,
pubmed-meshheading:20682795-HT29 Cells,
pubmed-meshheading:20682795-Histone Demethylases,
pubmed-meshheading:20682795-Humans,
pubmed-meshheading:20682795-Male,
pubmed-meshheading:20682795-MicroRNAs,
pubmed-meshheading:20682795-Middle Aged,
pubmed-meshheading:20682795-RNA, Messenger,
pubmed-meshheading:20682795-Transfection
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pubmed:year |
2010
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pubmed:articleTitle |
Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis.
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pubmed:affiliation |
Department of Internal Medicine, Division of Gastroenterology, Charles A Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, Texas 75246, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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