BRD7

Official Full Name

bromodomain containing 7

Organism

Homo sapiens

GeneID

29117

Background

This gene encodes a protein which is a member of the bromodomain-containing protein family. The product of this gene has been identified as a component of one form of the SWI/SNF chromatin remodeling complex, and as a protein which interacts with p53 and is required for p53-dependent oncogene-induced senescence which prevents tumor growth. Pseudogenes have been described on chromosomes 2, 3, 6, 13 and 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Synonyms

BP75; NAG4; CELTIX1; SMARCI1;

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Detailed Information

The bromodomain-containing protein 7 (BRD7), also known as the bromodomain protein of 75 kDa (BP75), is a member of the bromodomain-containing protein family. BRD7 is a key subunit of the PBAF (polybrominated-associated BRG1 related factor) chromatin remodeling complex that is involved in transcriptional regulation through interaction with acetylated histones in chromatin. BRD7 was originally identified as a tumor suppressor that inhibits the growth of nasopharyngeal carcinoma (NPC) cells by negatively regulating the β-catenin and extracellular regulated protein kinases (ERK) pathways. Recent studies have also shown that BRD7 acts as a tumor suppressor gene. For example, BRD7 inhibits tumorigenicity by recruiting chromatin remodeling complexes to the promoter of the target gene, affecting histone acetylation, p53 acetylation and promoter activity. BRD7 was also found to regulate BRCA1-dependent transcription by recruitment of BRCA1 and Oct-1 to the ESR1 promoter. In addition, BRD7 interacts directly with p85α, negatively regulating PI3K signaling, which maintains homeostatic cell growth. Moreover, various reports have confirmed that down-regulation of BRD7 expression is associated with various cancers. These findings clearly demonstrate the important role of BRD7 in tumor suppression and prognosis in cancer patients.

BRD7 and HCC

Hepatocellular carcinoma (HCC) is now the sixth most prevalent cancer in the world and the second most common cause of cancer-related deaths worldwide, especially in developing countries. Recently, some studies have found that BRD7 was down-regulated in tumor tissues and HCC cell lines. BRD7 protein expression was closely related to clinical stage and tumor size. Kaplan-Meier survival curves showed higher survival rates in patients with higher BRD7 expression levels than patients with lower BRD7 levels. Multivariate analysis indicated that BRD7 expression was an independent prognostic marker. Reintroduction of BRD7 expression significantly inhibited proliferation, colony formation, migration and invasion, and caused cell cycle arrest in HCC cells in vitro. In addition, mouse experiments indicate that BRD7 overexpression inhibits HCC tumorigenicity in vivo. Taken together, these data indicate that BRD7 can act as a tumor suppressor in HCC and can be a novel molecular target for the treatment of HCC.

BRD7 and breast cancer

Recently, some studies have found that BRD7 was down-regulated in breast cancer tissues and was identified as a poor prognostic factor for breast cancer. At the same time, BRD7 can inhibit cell proliferation, induce apoptosis and reduce aerobic glycolysis, indicating that BRD7 plays tumor suppressive roles in breast cancer. In a mechanism, BRD7 may be negatively regulated a critical glycolytic enzyme lactate dehydrogenase A (LDHA) through directly interaction with its upstream transcription factor, hypoxia-inducible factor 1α (HIF1α), facilitating degradation of HIF1a mediated by ubiquitin-proteasome pathway. In addition, restoring the expression of LDHA in breast cancer cells can reverse the effects of BRD7 on aerobic glycolysis, cell proliferation, and tumor formation, as well as expression of cell cycle and apoptosis-related molecules such as cyclin D1, CDK4, P21 and c-PARP both in vitro and in vivo. These results indicate that BRD7 plays a tumor suppressor role in breast cancer and inhibits glycolysis and tumor progression through the inactivation of the HIF1α/LDHA transcription axis.

BRD7 and NPC

Nasopharyngeal carcinoma (NPC) is the main form of malignant head and neck cancer in Southeast Asia, especially in southeastern China. Some study found that the expression of miR-141 was significantly increased in NPC tissues and was inversely correlated with the expression of BRD7 and the survival rate of NPC patients. The reduced expression levels of miR-141, including the primary, precursor and mature forms of miR-141, were found in BRD7-overexpressing HEK293, 5-8F and HNE1 cells compared the control cells, while there was no obvious effect on the expression levels of the two critical enzymes Drosha and Dicer. BRD7 can negatively regulate the promoter activity of miR-141, while no significant BRD7 binding site was found in the potential promoter region of miR-141. In addition, ectopic expression of miR-141 can significantly promote cell proliferation and inhibit NPC cell apoptosis, and rescuing miR-141 expression in BRD7-overexpressing NPC cells could partially reverse the tumor suppressive effect of BRD7 on cell proliferation and tumor growth in vitro and in vivo. Furthermore, activation of the PTEN/protein kinase B (AKT) pathway mediated by BRD7 overexpression can be inhibited by rescuing the expression of miR-141, and thus expression of miR-141 results in partial recovery of cell proliferation and tumor growth. These findings suggest that the BRD7/miR-141/PTEN/AKT axis plays a key role in the progression of NPC and provides some promising targets for the diagnosis and treatment of NPC.

Figure 1. BRD7 inhibited tumor growth by repressing miR-141/PTEN/AKT signaling. (Liu Y, et al. Cell Death and Disease, 2016)

BRD7 and NSCLC

Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma, accounts for approximately 85% of all lung cancer cases. Some study found that the expression of miR-410 was up-regulated in both human NSCLC tissues and cells. Overexpression of miR-410 promoted cell proliferation, migration and invasion of NSCLC. In addition, BRD7 was a direct target of miR-410. MiR-410-mediated down-regulation of BRD7 resulted in increased AKT phosphorylation. Inhibition of AKT phosphorylation can rescue the effect of miR-410 on NSCLC cells. Expression of BRD7 was down-regulated in NSCLC and inversely expressed with miC-410 in NSCLC.

In summary, current findings indicate that BRD7 is expressed as a tumor suppressor gene in a variety of cancers. However, the mechanism of occurrence and development of BRD7 in cancer is still unclear. Therefore, further study of the function of BRD7 and its important role in cancer will provide new insights and new directions for clinical medicine.

References:

Chen CL, et al. Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma. Oncotarget, 2016, 7: 13
Niu WH, et al. BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer. Cell Death and Disease, 2018, 9: 519
Liu Y, et al. miR-141 is involved in BRD7-mediated cell proliferation and tumor formation through suppression of the PTEN/ AKT pathway in nasopharyngeal carcinoma. Cell Death and Disease, 2016, 7: e2156
Liu YK, et al. BRD7 expression and c-Myc activation forms a double-negative feedback loop that controls the cell proliferation and tumor growth of nasopharyngeal carcinoma by targeting oncogenic miR-141. Research, 2018, 37:64
Li DR, et al. MicroRNA-410 promotes cell proliferation by targeting BRD7 in non-small cell lung cancer. FEBS Letters, 2015, 589: 2218-2223

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