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Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer

阿平添加于 2009-1-16 21:58 | 3573 次阅读 | 0 个评论

作者
Varambally S, Cao Q, Mani R-S, Shankar S, Wang X, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K, Brenner JC, Yu J, Kim JH, Han B, Tan P, Kumar-Sinha C, Lonigro RJ, Palanisamy N, Maher CA, Chinnaiyan AM
摘要
Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes and regulates the survival and metastasis of cancer cells. EZH2 is overexpressed in aggressive solid tumors by mechanisms that remain unclear. Here we show that the expression and function of EZH2 in cancer cell lines are inhibited by microRNA-101 (miR-101). Analysis of human prostate tumors revealed that miR-101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the two genomic loci encoding miR-101 were somatically lost in 37.5% of clinically localized prostate cancer cells (6 of 16) and 66.7% of metastatic disease cells (22 of 33). We propose that the genomic loss of miR-101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression.
详细资料
- 关键词: 3' Untranslated Regions; Algorithms; Breast Neoplasms/genetics/metabolism; Cell Line, Tumor; DNA-Binding Proteins/*genetics/metabolism; Disease Progression; Epigenesis, Genetic; Female; *Gene Expression Regulation, Neoplastic; Genome, Human; Histones/*metabolism; Humans; Lysine/metabolism; Male; Methylation; MicroRNAs/*genetics/metabolism; Neoplasm Metastasis; Neoplasms/*genetics/metabolism; Promoter Regions, Genetic; Prostatic Neoplasms/*genetics/metabolism/pathology; RNA, Small Interfering/gen
- 文献种类:期刊
- 期刊名称: Science (New York, N.Y.)
- 期卷页: 2008年第322卷第5908期 1695-1699页
- 地址: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- ISBN: 1095-9203
标签

EZH2 microRNA miR-101 表遗传
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