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Epigenetic regulation of microRNA expression in colorectal cancer
Author(s) -
Bandres Eva,
Agirre Xabier,
Bitarte Nerea,
Ramirez Natalia,
Zarate Ruth,
RomanGomez Jose,
Prosper Felipe,
GarciaFoncillas Jesus
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24638
Subject(s) - microrna , dna methylation , epigenetics , biology , gene silencing , cancer research , colorectal cancer , methylation , cpg site , carcinogenesis , dna methyltransferase , cancer epigenetics , regulation of gene expression , cancer , histone , gene expression , microbiology and biotechnology , genetics , gene
In the last years, microRNAs (miRNA) have emerged as new molecular players involved in carcinogenesis. Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown. To identify tumor‐supressor miRNAs silenced through aberrant epigenetic events in colorectal cancer (CRC), we used a sequential approach. We first identified 5 miRNAs down‐regulated in patient with colorectal cancer samples and located around/on a CpG island. Treatment with a DNA methyltransferase inhibitor and a HDAC inhibitor restored expression of 3 of the 5 microRNAs ( hsa‐miR‐9, hsa‐miR‐129 and hsa‐miR‐137 ) in 3 CRC cell lines. Expression of hsa‐miR‐9 was inversely correlated with methylation of their promoter regions as measure by MSP and bisulphate sequencing. Further, methylation of the hsa‐miR‐9‐1, hsa‐miR‐129 ‐2 and hsa‐miR‐137 CpG islands were frequently observed in CRC cell lines and in primary CRC tumors, but not in normal colonic mucosa. Finally, methylation of hsa‐miR‐9‐1 was associated with the presence of lymph node metastasis. In summary, our results aid in the understanding of miRNA gene regulation showing that aberrant DNA methylation and histone modifications work together to induce silencing of miRNAs in CRC. © 2009 UICC