Abstract
Bromodomain containing protein 4 (BRD4), a member of the bromodomain and extra terminal domain (BET) protein family, has been shown to play important roles in tumor progression. However, its role in non-small cell lung cancer (NSCLC) is still largely unknown. Here, we found that BRD4 expression was significantly upregulated in NSCLC tissues and NSCLC cell lines with higher invasion and metastasis potentials. Suppression of BRD4 expression in NSCLC cell lines impaired cell invasion, inhibited cell proliferation, and accelerated cell apoptosis. Clinically, we observed that the BRD4 level was significantly related to histological type, lymph node metastasis, tumor stage and differentiation. More importantly, high level of BRD4 was closely correlated with the poor prognosis of NSCLC patients. Therefore, our study suggests that BRD4 is one of the major contributors to the invasion-prone phenotype of NSCLC, and a potential therapeutic target of NSCLC.
Highlights
Lung cancer is the first leading cause of cancerrelated deaths worldwide [1]
Bromodomain containing protein 4 (BRD4) highly expresses in non-small cell lung cancer (NSCLC) tissues and NSCLC cell lines with higher invasion and metastasis potentials
We found that the BRD4 staining was localized to the nucleus, and the expression of BRD4 in NSCLC tissues was stronger than that in their corresponding adjacent normal lung tissues (Figure 1C), and the difference was significant (Figure 1D)
Summary
Lung cancer is the first leading cause of cancerrelated deaths worldwide [1]. The non-small cell lung cancer (NSCLC), which accounts for about 85% of lung cancers, is the most common type of lung cancers. BRD4 is the best-studied member of the BET family and it plays an important role in various biological processes by means of its two bromodomains (BRDs). It links cell cycle and transcription, bookmarking active genes during mitosis and serving as a scaffold for transcription factors. Recent studies have showed that BRD4 activation may predict the overall survival of patients with several tumors, such as melanoma, hepatocellular carcinoma, multiple myeloma, Burkitt’s lymphoma, acute myeloid leukemia and breast cancer [12,13,14,15,16,17]
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