The role of bromodomain-containing protein 4 in the replication human papillomavirus, apoptosis, proliferation and migration of cervical cancer cells.

We investigated the correlation between bromodomain-containing protein 4 (BRD4) and HPV16 viral load in cervical squamous cell carcinoma and non-cancerous tissues, as well as the effects of BRD4 degradation regent MZ1 on the viral load, proliferation and migration of cervical cancer cells. Real-time fluorescence quantitative PCR showed that the viral load of cervical cancer specimens was significantly higher than that of non-cancer specimens. Immunohistochemical assay showed that BRD4 expression was elevated in cervical cancer specimens (P < 0.001) and in specimens with high viral load (P < 0.0001). Treatment of cervical cancer cells of SiHa, HeLa and CaSki with BRD4 degradation regent MZ1 significantly reduced viral load and inhibited cell proliferation and migration. Nude mouse xenograft tumor confirmed that the tumor volume, and tumor weight of the MZ1-treated mice were significantly lower than those of the control group. Expression of BRD4 and cell proliferation molecule Ki67 in the tumor sections of MZ1-treated mice was significantly decreased, while apoptosis molecule cleaved caspase-3 expression was significantly increased. Moreover, the viral load in the MZ1-treated group was significantly lower than that in the control group. These findings suggest that BRD4 has a potential role in HPV16 viral replication, and MZ1 has a favorable effect in inhibiting viral replication, increasing apoptosis and suppressing the proliferation and migration of cervical cancer cells.