Identification of GRB2 and GAB1 Coexpression as an Unfavorable Prognostic Factor for Hepatocellular Carcinoma by a Combination of Expression Profile and Network Analysis

Zhang, Yanqiong; Li, Zhiwei; Yang, Mei; Wang, Danhua; Yu, Lingxiang; Guo, Chaonan; Guo, Xiaodong; Lin, Na

doi:10.1371/journal.pone.0085170

Cited by 67 publications

(51 citation statements)

References 49 publications

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“…This hypothesis is supported by the fact that EZH2 was shown to has a key role in the regulation of tumor angiogenesis and the decrease in its expression levels inhibited metastasis suggesting EZH2 as a potential therapeutic target to reverse the migration and invasion of cancer cells [40][41][42][43][44]. Like VCAN and EZH2 genes, several studies have shown that Grb2 has an important role in proliferation and angiogenesis of several tumors including HCC through its contribution in the signaling pathway of various angiogenic factors [17,22,45,46]. The overexpression of miR-564 was shown to inhibit the proliferation, migration and invasion of HCC cell lines through a direct effect on Grb2 gene [46].…”

Section: Discussionmentioning

confidence: 97%

“…A cytoplasmic expression of VCAN protein was shown to be upregulated in HCC compared to matched normal tissues [19] and this overexpression was suggested as candidate biomarker for early stages of HCC [20]. In the same context, high expression of EZH2 [21] and Grb2 genes [22] were detected in HCC and also suggested as a promising diagnostic biomarkers of HCC.…”

Section: Introductionmentioning

confidence: 91%

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Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

et al. 2019

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Human hepatocellular carcinoma (HCC) is the most prevalent and recurrent type of primary adult liver cancer without any effective therapy. Thus, there is an increase demands for finding new drugs and treatment strategies with selective and potent effects towards HCC. Plant-derived compounds acting as anti-cancer agents can induce apoptosis through targeting several signaling pathways. Thymoquinone (TQ), the major biologically active compound of the black seed oil (Nigella sativa) has demonstrated inhibitory activities on various cancers by targeting several pathways. In the present study, we have evaluated the molecular mechanisms that underlie the anti-proliferative, anti-metastatic, and pro-apoptotic activities exerted by TQ on liver cancer cell lineHepG2, a well-documented HCC in vitro model. Cell proliferation was determined by WST-1 assay, apoptosis rate was assessed by flow cytometry using annexin-V/7AAD staining, wound healing assay to investigate the metastasis, and the expression of target genes was assessed by Real-time RT–PCR analysis. We found that TQ significantly reduced HepG2 cell viability and induced apoptosis in a dose-dependent manner. Migration of HepG2 cells was suppressed in response to TQ. Moreover, TQ decreased the expression of several angiogenesis-related genes including versican (VCAN), growth factor receptor-bound protein 2 (Grb2), and the histone methyltransferase for lysine 27 of histone 3 (EZH2). The findings suggest that TQ exerts inhibitory effects on HCC most likely through targeting key genes involved in the invasiveness and

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 91%

Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

et al. 2019

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“…Gene Ontology (GO) and Signaling Pathway Analysis GO analysis and signaling pathway analysis for the targets were analyzed through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). 25) The results were assigned into 3 categories: biological processes, molecular function, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis. p ≤ 0.05 was regarded as significance.…”

Section: Networkmentioning

confidence: 99%

To Elucidate the Inhibition of Excessive Autophagy of <i>Rhodiola crenulata</i> on Exhaustive Exercise-Induced Skeletal Muscle Injury by Combined Network Pharmacology and Molecular Docking

Hou

Wang

et al. 2020

Biological & Pharmaceutical Bulletin

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Autophagy can remodel skeletal muscle in response to exercise. However, excessive autophagy can have adverse effects on skeletal muscle. Although Rhodiola crenulata (R. crenulata) is thought to regulate autophagy, its active ingredients and mechanisms of action remain unclear. In this study, molecular docking and network pharmacology were used to screen for autophagy-related targets of R. crenulata. Subsequently, protein-protein interaction (PPI) analysis was used to find the relationships between the inverse docking targets and autophagy-related targets and therefore highlight the key targets. And then the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database was recruited to explain the functions and enrichment pathways of the target proteins. Finally, the potential targets were validated by immunohistochemistry of a mouse model of exhaustive exercise-induced skeletal muscle injury. We found a network of 15 major constituents of R. crenulata with 30 autophagy-related and 105 inverse-docking targets by molecular docking and network pharmacology. The results of PPI analysis indicated that 16 inverse-docking targets interacted 8 autophagy-related proteins. Further pathway analysis showed that R. crenulata could regulate exerciseinduced skeletal muscle autophagy through mammalian target of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Forkhead box protein O (FoxO). The results of our animal experiments indicated that R. crenulata could suppress the expression of Ubiquitin-like protein ATG12 (ATG12), Beclin-1 (BECN1), and Serine/threonine-protein kinase ULK1 (ULK1), while increasing the expression of MTOR, NAD-dependent protein deacetylase sirtuin-1 (SIRT1), and Microtubule-associated protein tau (MAPT). In conclusion, this study demonstrated that R. crenulata may protect skeletal muscle injury induced by exhaustive exercise via regulating the mTOR, AMPK, and FoxO singling pathway.

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“…Centiscape [15], the app of Cytoscape, was used to calculate the degree measure of each node. Referring to the previous study of others [16,17], we determined the nodes whose degree were more than twice the mean degree value as hub genes. In order to explore more specific regulatory relationship in the above PPI network, the cluster analysis was performed by MCODE [18].…”

Section: The Construction and Analyzing Of Ppi Networkmentioning

confidence: 99%

Discovery of potential drugs for COVID-19 based on the connectivity map

Li¹,

Bai²,

Yang³

et al. 2020

Preprint

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Background: Corona virus infective disease 19 is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spreads very rapidly, which become a worldwide public healthy crisis. Until now, there is no effective antivirus drugs or vaccines specifically used for its treatment. So it is urgent to discover efficient therapeutic methods. The same as SARS-CoV, SARS-CoV-2 also invades organism by combining with Angiotensin-converting enzyme 2 (ACE2). Recently, there are reports about SARS-CoV-2 infected host not only through the respiratory tract, but also gastrointestinal tract. However, it is proved that ACE2 plays a key role in protecting subjects from lung injury and resisting the inflammation caused by intestinal epithelial damage. Interestingly, the expression of ACE2 protein is reduced after SARS-CoV infection.Methods: According to the dataset of genes co-expressed with ACE2 in the colonic epithelial cells, we established a protein-protein interaction (PPI) Network and selected hub genes from them. The cluster analysis was performed to find out the dense region of the PPI Network. Then, gene ontology (GO) and pathway enrichment analysis were performed to explore the main function of genes co-expressed with ACE2. Finally, we predicted the potential drugs for the treatment of COVID-19 based on the connectivity map (Cmap) .Results: We constructed a PPI network containing 125 hub genes of genes co-expressed with ACE2 in the colonic epithelial cells and obtained two modules through cluster analysis. The GO analysis and the KEGG pathway revealed these genes were aggregated in ribosome, exosomes, extracellular cellular components; structure constituent of ribosome, G-protein coupled receptor activity, MHC class I and II receptor activity biological processes; immune response, protein metabolism, signal transduction biological processes; and ribosome, graft-versus-host disease, viral myocarditis pathways. The result

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Identification of GRB2 and GAB1 Coexpression as an Unfavorable Prognostic Factor for Hepatocellular Carcinoma by a Combination of Expression Profile and Network Analysis

Cited by 67 publications

References 49 publications

Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

To Elucidate the Inhibition of Excessive Autophagy of <i>Rhodiola crenulata</i> on Exhaustive Exercise-Induced Skeletal Muscle Injury by Combined Network Pharmacology and Molecular Docking

Discovery of potential drugs for COVID-19 based on the connectivity map

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