Dataset Information

AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-?B signaling pathway in hepatocellular carcinoma.

ABSTRACT: High levels of angiogenesis and resistance to apoptosis are major clinical features of hepatocellular carcinoma (HCC), a lethal disease with a high incidence worldwide. However, the precise mechanisms underlying these malignant properties remain unclear. Here, we demonstrated that acylglycerol kinase (AGK) is markedly overexpressed in HCC cell lines and clinical tissues. Immunohistochemical analysis of 245 clinical HCC specimens revealed patients with high levels of AGK expression had poorer overall survival compared to patients with low AGK expression. Furthermore, overexpressing AGK significantly enhanced angiogenesis and inhibited apoptosis in vitro and promoted the tumorigenicity of HCC cells in vivo; silencing endogenous AGK had the opposite effects. Importantly, AGK enhanced angiogenesis and inhibited apoptosis in HCC in part via activation of NF-?B signaling. Our findings provide new evidence that AGK plays an important role in promoting angiogenesis and providing resistance to apoptosis, thus AGK may represent a novel therapeutic target for HCC.

SUBMITTER: Cui Y

PROVIDER: S-EPMC4323001 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-κB signaling pathway in hepatocellular carcinoma.

Cui Yanmei Y Lin Chuyong C Wu Zhiqiang Z Liu Aibin A Zhang Xin X Zhu Jinrong J Wu Geyan G Wu Jueheng J Li Mengfeng M Li Jun J Song Libing L

Oncotarget 20141201 23

High levels of angiogenesis and resistance to apoptosis are major clinical features of hepatocellular carcinoma (HCC), a lethal disease with a high incidence worldwide. However, the precise mechanisms underlying these malignant properties remain unclear. Here, we demonstrated that acylglycerol kinase (AGK) is markedly overexpressed in HCC cell lines and clinical tissues. Immunohistochemical analysis of 245 clinical HCC specimens revealed patients with high levels of AGK expression had poorer ove ...[more]

PMID: 25474138

Similar Datasets

Project description:Simple Summary Pseudorabies virus (PRV) is a herpesvirus with zoonotic potential and has caused significant economic losses to the global pig industry. With the emergence of new mutants, the immune protection provided by vaccines has been greatly reduced, and it has become more difficulty to control PRV by vaccination. Recently, human cases of PRV-induced encephalitis have been reported, which suggest an urgent need for new control measures. In this study, we found that dihydromyricetin (DMY) exerted potent antiviral activity against PRV in vitro. DMY could ameliorate the PRV-induced abnormal activation of the NF-κB signaling pathway and excessive cellular inflammatory response. DMY could also induce the apoptosis of PRV-infected cells, thereby limiting the production of progeny virus. Based on the findings, DMY could be a candidate drug for the treatment of PRV infections. Abstract Pseudorabies virus (PRV) infections have caused huge economic losses to the breeding industry worldwide, especially pig husbandry. PRV could threaten human health as an easily ignored zoonotic pathogen. The emergence of new mutants significantly reduced the protective effect of vaccination, indicating an urgent need to develop specific therapeutic drugs for PRV infection. In this study, we found that dihydromyricetin (DMY) could dose-dependently restrain PRV infection in vitro with an IC50 of 161.34 μM; the inhibition rate of DMY at a concentration of 500 μM was 92.16 %. Moreover, the mode of action showed that DMY directly inactivated PRV virion and inhibited viral adsorption and cellular replication. DMY treatment could improve PRV-induced abnormal changes of the NF-κB signaling pathway and excessive inflammatory response through regulation of the contents of IκBα and p-P65/P65 and the transcriptional levels of cytokines (TNF-α, IL-1β and IL-6). Furthermore, DMY promoted the apoptosis of PRV-infected cells through the regulation of the expressions of Bax and Bcl-xl and the transcriptional levels of Caspase-3, Bax, Bcl-2 and Bcl-xl, thereby limiting the production of progeny virus. These findings indicated that DMY could be a candidate drug for the treatment of PRV infection.

Project description:Microglia, the brain-resident macrophage, is known as the innate immune cell type in the central nervous system. Microglia is also the major cellular component of tumor mass of gliomas that plays a key role in glioma development. Mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2) frequently occur in gliomas, which leads to accumulation of oncometabolic product 2-hydroxyglutarate (2HG). Moreover, IDH1/2 mutations were found to correlate with better prognosis in glioma patients. In the present study, we investigated the effects of the 2HG on microglial inflammatory activation. We showed that the conditioned media (CM) from GL261 glioma cells stimulated the activation of BV-2 microglia cells, evidenced by markedly increased expression of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), CCL2 (C-C motif chemokine ligand 2) and CXCL10 (C-X-C motif chemokine 10). CM-induced expression of proinflammatory genes was significantly suppressed by pretreatment with a synthetic cell-permeable 2HG (1 mM) or a nuclear factor-κB (NF-κB) inhibitor BAY11-7082 (10 μM). In lipopolysaccharide (LPS)- or TNF-α-stimulated BV-2 microglia cells and primary microglia, pretreatment with 2HG (0.25-1 mM) dose-dependently suppressed the expression of proinflammatory genes. We further demonstrated that 2HG significantly suppressed LPS-induced phosphorylation of IκB kinase α/β (IKKα/β), IκBα and p65, IκB degradation, and nuclear translocation of p65 subunit of NF-κB, as well as NF-κB transcriptional activity. Similarly, ectopic expression of mutant isocitrate dehydrogenase 1 (IDH1) (R132H) significantly decreased TNF-α-induced activation of NF-κB signaling pathway. Finally, we revealed that activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and subsequent inhibition of mammalian target of rapamycin (mTOR) signaling contributed to the inhibitory effect of 2HG on NF-κB signaling pathway in BV-2 cells. Taken together, these results, for the first time, show that oncometabolite 2HG inhibits microglial activation through affecting AMPK/mTOR/NF-κB signaling pathway and provide evidence that oncometabolite 2HG may regulate glioma development via modulating microglial activation in tumor microenvironment.

Dataset Information

AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-?B signaling pathway in hepatocellular carcinoma.

Publications

AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-κB signaling pathway in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets