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

Overview

Journal Science

Specialty Science

Date 2008 Nov 15

PMID 19008416

Citations 510

Authors

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

Affiliations

Soon will be listed here.

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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