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

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

doi:10.1126/science.1165395

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

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

Houston Methodist

Research output: Contribution to journal › Article › peer-review

940 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1695-1699
Number of pages	5
Journal	Science
Volume	322
Issue number	5908
DOIs	https://doi.org/10.1126/science.1165395
State	Published - Dec 12 2008

ASJC Scopus subject areas

General

Access to Document

10.1126/science.1165395

Cite this

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, 322(5908), 1695-1699. https://doi.org/10.1126/science.1165395

Varambally, S, Cao, Q, Mani, RS, 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 2008, 'Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer', Science, vol. 322, no. 5908, pp. 1695-1699. https://doi.org/10.1126/science.1165395

@article{82311dc0a6e747249b3dca5b2ccdd379,

title = "Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer",

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.",

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

year = "2008",

month = dec,

day = "12",

doi = "10.1126/science.1165395",

language = "English (US)",

volume = "322",

pages = "1695--1699",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5908",

}

TY - JOUR

T1 - Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer

AU - Varambally, Sooryanarayana

AU - Cao, Qi

AU - Mani, Ram Shankar

AU - Shankar, Sunita

AU - Wang, Xiaosong

AU - Ateeq, Bushra

AU - Laxman, Bharathi

AU - Cao, Xuhong

AU - Jing, Xiaojun

AU - Ramnarayanan, Kalpana

AU - Brenner, J. Chad

AU - Yu, Jindan

AU - Kim, Jung H.

AU - Han, Bo

AU - Tan, Patrick

AU - Kumar-Sinha, Chandan

AU - Lonigro, Robert J.

AU - Palanisamy, Nallasivam

AU - Maher, Christopher A.

AU - Chinnaiyan, Arul M.

PY - 2008/12/12

Y1 - 2008/12/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=58149239686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149239686&partnerID=8YFLogxK

U2 - 10.1126/science.1165395

DO - 10.1126/science.1165395

M3 - Article

C2 - 19008416

AN - SCOPUS:58149239686

SN - 0036-8075

VL - 322

SP - 1695

EP - 1699

JO - Science

JF - Science

IS - 5908

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this