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.
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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 -