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

British journal of cancer (2020-06-06)
Tatsuro Yamamoto, Akiyuki Hirosue, Masafumi Nakamoto, Ryoji Yoshida, Junki Sakata, Yuichiro Matsuoka, Kenta Kawahara, Yuka Nagao, Masashi Nagata, Nozomu Takahashi, Akimitsu Hiraki, Masanori Shinohara, Mitsuyoshi Nakao, Noriko Saitoh, Hideki Nakayama

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. We investigated the role of BRD4 and its potential utility as a therapeutic target in OSCC. 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. 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.

Product Number
Product Description

Monoclonal Anti-β-Tubulin antibody produced in mouse, clone TUB 2.1, ascites fluid
(-)-JQ1, ≥95% (HPLC)

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