BioProject

Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high malignant potential, including metastasis, affects patient survival. More...

Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high malignant potential, including metastasis, affects patient survival. Bromodomain containing 4 (BRD4) is a chromatin protein that recognizes and associates with acetylated histone lysines, and facilitates transcriptional activation. 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. Herein, we investigated the role of BRD4­ and the potential utility of BRD4­ as a therapeutic target in OSCC. JQ1, which inhibits the interaction between BRD4 and acetylated histones, suppressed the proliferation, migration, and invasion of OSCC cell lines. JQ1 reduced the expression levels of 15 metastasis genes in OSCC, including the Matrix Metallopeptidase 2 (MMP2) gene. Interestingly, our chromatin immunoprecipitation assay showed that JQ1 reduced the BRD4 binding to the histone H3 lysine 27 acetylation-enriched sites in the MMP2 locus. Finally, qRT-PCR 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. These results suggest that 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. Overall design: The gene expression in HOC313 cells was measured at 48 hours treated with JQ1 (1.0 μM) or vehicle. Less...