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

By S. Varambally, Q. Cao, R. Mani, Sunita Shankar, Xiaosong Wang, Bushra Ateeq, B. Laxman, Xuhong Cao, Xiaojun Jing, Kalpana Ramnarayanan and 10 more. Science, 2008

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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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/844ee9ea25054273b6e7f864de21402e3e141abd

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Citations in the corpus

EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations (2012, background): “Under these conditions, the contribution from the enzyme concentration becomes relatively small (see equation (1)) and accurate estimates of Ki can be calculated(29).”
Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. (2010, positive): “In addition, PcG proteins have been shown to be recruited to target genes by physically interacting with a number of chimeric fusion proteins involved in leukemia, such as PLZF-RARA and TMPRSS2-ERG (Figure 5D) (Boccuni et al., 2003; Boukarabila et al., 2009; Garcı́a-Cuéllar et al., 2001; Hemenway et”
A decade of exploring the cancer epigenome — biological and translational implications (2011, background): “miR-101 is often downregulated in cancer, leading to overexpression of enhancer of zeste 2 (EZH2”
MicroRNAs — the micro steering wheel of tumour metastases (2009, background): “An additional example of the potential dual role of miRNAs in stemness and metastasis is represented by miR-101-1 (Ref”
Polycomb group proteins: navigators of lineage pathways led astray in cancer (2009, positive): “Potentially contributing to these increased EZH2 levels, the microRNA miR-101 has recently been reported to directly target EZH2 and is itself deleted in some cancer”
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