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Cited by 1,052

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Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer

Open access
Varambally, Sooryanarayana, Cao, Qi, Mani, Ram-Shankar, Shankar, Sunita, Wang, Xiaosong, Ateeq, Bushra, Laxman, Bharathi, Cao, Xuhong, Jing, Xiaojun, Ramnarayanan, Kalpana, Brenner, J. Chad, Yu, Jindan, Kim, Jung H., Han, Bo, Tan, Patrick, Kumar-Sinha, Chandan, Lonigro, Robert J., Palanisamy, Nallasivam, Maher, Christopher A., Chinnaiyan, Arul M.·2008·Science

Abstract

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.

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Metadata

Authors
Varambally, S., Cao, Q., Mani, R.-S., Shankar, S., Wang, X., Ateeq, B., Laxman, B., Cao, X., Jing, X., Ramnarayanan, K., Brenner, J. C., Yu, J., Kim, J. H., Han, B., Tan, P., Kumar-Sinha, C., Lonigro, R. J., Palanisamy, N., Maher, C. A., & Chinnaiyan, A. M.
Venue
Science
Published
2008-12-12
Volume
322
Issue
5908
Pages
1695-1699
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2040182688
Cited by
1,052
References
8
FWCI
23.85
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer. https://app.cochat.ai/papers/10.1126/science.1165395
The paper
Varambally, S., Cao, Q., Mani, R.-S., Shankar, S., Wang, X., Ateeq, B., Laxman, B., Cao, X., Jing, X., Ramnarayanan, K., Brenner, J. C., Yu, J., Kim, J. H., Han, B., Tan, P., Kumar-Sinha, C., Lonigro, R. J., Palanisamy, N., Maher, C. A., & Chinnaiyan, A. M. (2008). Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer. Science. https://doi.org/10.1126/science.1165395

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.