Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer (Science, 2008, 322:1695-1699)

報告日期: 2009/03/13
報告時間: 16:00/16:50
報告學生: 鄧喬方
講評老師: 呂佩融
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980313-2.pdf

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

 

Science 322, 1695-1699 (2008)

 

Speaker: 鄧喬方

Commentator: 呂佩融 老師

Date: 2009.3.13, pm 4:00-4:50

Place: room 602

 

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. MicroRNAs (miRNAs) have gained considerable attention as regulators of gene expression. Recent studies have also demonstrated that alterations in miRNA genes lead to tumor formation. In this study, the authors found that the expression of EZH2 transcript and protein in cancer cell lines was inhibited by microRNA-101 (miR-101). The result from in vitro cell proliferation, invasion, and in vivo tumor growth assays showed that EZH2-mediated function was also inhibited by miR-101. Furthermore, miR-101 overexpression resulted in decreased overall H3K27 trimethylation and increased transcript expression of EZH2 target genes. Analysis of human prostate tumors revealed that miR-101 expression decreased during cancer progression, paralleling an increase in EZH2 expression. One or both of the two genomic loci encoding miR-101 were somatically lost in clinically localized prostate cancer and most pronounced in metastatic disease cells. These data indicate that the genomic loss of miR-101 in cancer may lead to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression. Moreover, approaches to reintroduce miR-101 into tumors may have therapeutic benefit by reverting

the epigenetic program of tumor cells to a more normal state.

 

References:

1.  Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.

2.  Simon JA and Lange CA (2008). Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res 647, 21-29.