Bromodomain containing protein represses the Ras/Raf/MEK/ERK pathway to attenuate human hepatoma cell proliferation during HCV infection

Zhang, Qi; Liang, Wei; Yang, Hongchuan; Yang, Wanqi; Yang, Qingyu; Zhang, Zhuofan; Wu, Kailang

doi:10.1016/j.canlet.2015.11.027

Cited by 35 publications

(24 citation statements)

References 41 publications

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“…ERK1/2 is strongly activated by HG stimulation [35]. A recent study showed that activation of Ras/Raf/MEK/ERK pathway increased BRD7 expression in hepatoma cell during HCV infection [36]. Then, we investigated whether HG-induced activation of ERK1/2 facilitated the expression of BRD7 in H9c2 cardiomyoblasts.…”

Section: Discussionmentioning

confidence: 98%

BRD7 mediates hyperglycaemia‐induced myocardial apoptosis via endoplasmic reticulum stress signalling pathway

Wang

Liu

et al. 2016

J Cellular Molecular Medi

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Bromodomain‐containing protein 7 (BRD7) is a tumour suppressor that is known to regulate many pathological processes including cell growth, apoptosis and cell cycle. Endoplasmic reticulum (ER) stress‐induced apoptosis plays a key role in diabetic cardiomyopathy (DCM). However, the molecular mechanism of hyperglycaemia‐induced myocardial apoptosis is still unclear. We intended to determine the role of BRD7 in high glucose (HG)‐induced apoptosis of cardiomyocytes. In vivo, we established a type 1 diabetic rat model by injecting a high‐dose streptozotocin (STZ), and lentivirus‐mediated short hairpin RNA (shRNA) was used to inhibit BRD7 expression. Rats with DCM exhibited severe myocardial remodelling, fibrosis, left ventricular dysfunction and myocardial apoptosis. The expression of BRD7 was up‐regulated in the heart of diabetic rats, and inhibition of BRD7 had beneficial effects against diabetes‐induced heart damage. In vitro, H9c2 cardiomyoblasts was used to investigate the mechanism of BRD7 in HG‐induced apoptosis. Treating H9c2 cardiomyoblasts with HG elevated the level of BRD7 via activation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and increased ER stress‐induced apoptosis by detecting spliced/active X‐box binding protein 1 (XBP‐1s) and C/EBP homologous protein (CHOP). Furthermore, down‐regulation of BRD7 attenuated HG‐induced expression of CHOP via inhibiting nuclear translocation of XBP‐1s without affecting the total expression of XBP‐1s. In conclusion, inhibition of BRD7 appeared to protect against hyperglycaemia‐induced cardiomyocyte apoptosis by inhibiting ER stress signalling pathway.

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Section: Discussionmentioning

confidence: 98%

BRD7 mediates hyperglycaemia‐induced myocardial apoptosis via endoplasmic reticulum stress signalling pathway

Wang

Liu

et al. 2016

J Cellular Molecular Medi

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“…The ERK1/2 cell signaling pathway is a well known cell proliferation signal as is the PI3K/AKT cell signaling pathway. In various tumors, down‐regulation of ERK1/2 MAPK signaling inhibits proliferation and migration of cells and also induces apoptosis of cells including prostate cancer cells [Park et al, ; Zhang et al, ]. Inhibition of P38 MAPK by TNF‐α specifically induces apoptosis of prostate cancer cells [Gil‐Araujo et al, ]; however, the level and subtype of JNK inducing apoptosis is very controversial.…”

Section: Discussionmentioning

confidence: 99%

Naringenin‐Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways

Lim

Park

Bazer

et al. 2017

J of Cellular Biochemistry

120

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Prostate cancer is the most common cancer in men and the second most common cause of cancer-related deaths in men. Although, various drugs targeting the androgen receptor are normally used, the patients frequently undergo recurrence of the disease. To overcome these limitations, natural compounds have been researched for evidence that they suppress progression and metastasis of various cancer cells. In the present study, we investigated effects of naringenin, a natural anti-oxidant flavonoid derived from citrus, on prostate cancer cells (PC3 and LNCaP). Results of present study with PC3 and LNCaP cells revealed that naringenin inhibited proliferation and migration, while inducing apoptosis and ROS production by those cells. In addition, naringenin-induced loss of mitochondrial membrane potential and increased Bax and decreased Bcl-2 proteins in PC3 cells, but not LNCaP cells. In a dose-dependent manner, naringenin decreased phosphorylation of ERK1/2, P70S6K, S6, and P38 in PC3 cells, and reduced phosphorylation of ERK1/2, P53, P38, and JNK proteins in LNCaP cells. However, naringenin activated phosphorylation of AKT in both PC3 and LNCaP cells. Then, targeted signaling proteins associated with viability of PC3 and LNCaP cells were analyzed using pharmacological inhibitors of AKT and ERK1/2 cell signaling pathways. Moreover, we compared the apoptotic effects of naringenin and paclitaxel alone and in combination to find that naringenin enhanced the efficiency of paclitaxel to suppress progression of prostate cancer cell lines. Collectively, these results indicate that naringenin is a potential chemotherapeutic agent for treatment of prostate cancer. J. Cell. Biochem. 118: 1118-1131, 2017. © 2016 Wiley Periodicals, Inc.

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“…Upregulation of BRD7, in contrast, leads to differential expression of 12 genes that are involved in the MAPK/ERK and Rb/E2F signaling cascades [ 27 ]: these include the downregulation of MEK1, GRB2, and E2F3, and upregulation of CDC42. This suggests that BRD7 is involved in cell proliferation [ 28 ] and that the suppression of cell cycle progression by BRD7 occurs via the transcriptional regulation of key proteins involved in the cell cycle. Further studies in HNE1 NPC cells as well as COS7 cells show that BRD7 is localized primarily in the nucleus, and contains a nuclear localization signal (NLS) from amino acid residues 65 to 96 [ 81 ].…”

Section: Brd7 In Cancermentioning

confidence: 99%

Emerging Roles of BRD7 in Pathophysiology

Park

Lee

2020

IJMS

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Bromodomain is a conserved structural module found in many chromatin-associated proteins. Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family, and was discovered two decades ago as a protein that is downregulated in nasopharyngeal carcinoma. Since then, BRD7 has been implicated in a variety of cellular processes, including chromatin remodeling, transcriptional regulation, and cell cycle progression. Decreased BRD7 activity underlies the pathophysiological properties of various diseases in different organs. BRD7 plays an important role in the pathogenesis of many cancers and, more recently, its roles in the regulation of metabolism and obesity have also been highlighted. Here, we review the involvement of BRD7 in a variety of pathophysiological conditions, with a focus on glucose homeostasis, obesity, and cancer.

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Bromodomain containing protein represses the Ras/Raf/MEK/ERK pathway to attenuate human hepatoma cell proliferation during HCV infection

Cited by 35 publications

References 41 publications

BRD7 mediates hyperglycaemia‐induced myocardial apoptosis via endoplasmic reticulum stress signalling pathway

BRD7 mediates hyperglycaemia‐induced myocardial apoptosis via endoplasmic reticulum stress signalling pathway

Naringenin‐Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways

Emerging Roles of BRD7 in Pathophysiology

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