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BRD4 promotes metastatic potential in oral squamous cell carcinoma through the epigenetic regulation of the MMP2 gene.

Abstract：

BACKGROUND:Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high metastatic potential affects patient survival. Bromodomain containing 4 (BRD4) is a chromatin protein that associates with acetylated histone lysines and facilitates transcription. BRD4 has been implicated in cell proliferation, metastasis, and prognosis in several types of cancer. However, the role of BRD4 in OSCC remains to be elucidated. METHODS:We investigated the role of BRD4 and its potential utility as a therapeutic target in OSCC. RESULTS:JQ1, the BRD4 inhibitor, suppressed the cell proliferation, migration, and invasion in the OSCC cell lines and in vivo. JQ1 reduced the expression levels of 15 metastasis genes in OSCC, including matrix metallopeptidase 2 (MMP2). Our chromatin immunoprecipitation assay showed that JQ1 reduced the BRD4 binding to the histone H3 lysine 27 acetylation-enriched sites in the MMP2 locus. Analyses of biopsy specimens from OSCC patients revealed that the BRD4 and MMP2 expression levels were correlated in the cancerous regions, and both were highly expressed in lymph node metastasis cases, including delayed metastasis. CONCLUSIONS:BRD4 contributes to metastasis in OSCC, through the epigenetic regulation of the MMP2 gene, and thus BRD4 may represent a therapeutic target and a novel prediction indicator for metastasis.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Yamamoto T,Hirosue A,Nakamoto M,Yoshida R,Sakata J,Matsuoka Y,Kawahara K,Nagao Y,Nagata M,Takahashi N,Hiraki A,Shinohara M,Nakao M,Saitoh N,Nakayama H

doi

10.1038/s41416-020-0907-6

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

580-590

issue

4

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-020-0907-6

journal_volume

123

pub_type

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