Elevated expression of sepiapterin reductase, regulator of G protein signaling 1, hypothetical protein CXorf58 homolog, and zinc finger and BTB domain–containing protein 21 isoform X2 is associated with progression of hepatocellular carcinoma

The aim of this study was to investigate the role of G-protein signaling modulator 2 in the carcinogenesis and progression of hepatocellular carcinoma. We previously showed that G-protein signaling modulator 2 was upregulated in hepatitis B virus-related hepatocellular carcinoma tissues through a hierarchical clustering analysis. With this study, we first assessed the expression pattern of G-protein signaling modulator 2 in hepatocellular carcinoma specimens and adjacent noncancerous tissues; clinical data were analyzed, along survival times, utilizing the Kaplan–Meier method. Moreover, the functions of G-protein signaling modulator 2 were examined using small-interfering RNAs in vitro. The results showed that G-protein signaling modulator 2 was clearly overexpressed in hepatocellular carcinoma tissues and cell lines and that the G-protein signaling modulator 2 expression level was related to tumor size and hepatitis B virus infection. Furthermore, G-protein signaling modulator 2 knockdown studies suggested that G-protein signaling modulator 2 accelerates cell growth, cell cycle, migration, and invasion and inhibits apoptosis, acting as an oncogene in hepatocellular carcinoma. Western blotting indicated that silencing of G-protein signaling modulator 2 in HepG2 and SMMC-7721 cells increased the expression levels of Bax, caspase-3, and E-cadherin, while notably suppressing the cyclin-dependent kinase 4, cyclin-dependent kinase 6, CyclinD1, Snail1, Vimentin, and matrix metallopeptidase 9 expression levels, compared with that in the control groups. In addition, we found that G-protein signaling modulator 2 can affect the expression of key proteins involved in protein kinase B activation. In conclusion, high expression of G-protein signaling modulator 2 was involved in the pathological processes of hepatocellular carcinoma through activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which may provide an attractive potential diagnostic biomarker and therapeutic target for treatment of hepatocellular carcinoma.

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Over-expression of regulator of G protein signaling 5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells

Journal of Surgical Oncology ◽

10.1002/jso.23367 ◽

2013 ◽

Vol 108 (3) ◽

pp. 192-196 ◽

Cited By ~ 18

Author(s):

Minghua Hu ◽

Xiaobing Chen ◽

Jianmin Zhang ◽

Dong Wang ◽

Xiaosan Fang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

G Protein ◽

Tumor Metastasis ◽

Epithelial Mesenchymal Transition ◽

Carcinoma Cells ◽

G Protein Signaling ◽

Protein Signaling ◽

Hepatocellular Carcinoma Cells ◽

Mesenchymal Transition ◽

Over Expression

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Altered expression and function of regulator of G-protein signaling-17 (RGS17) in hepatocellular carcinoma

Cellular Signalling ◽

10.1016/j.cellsig.2011.05.012 ◽

2011 ◽

Vol 23 (10) ◽

pp. 1603-1610 ◽

Cited By ~ 14

Author(s):

Eugene Sokolov ◽

David A. Iannitti ◽

Laura W. Schrum ◽

Iain H. McKillop

Keyword(s):

Hepatocellular Carcinoma ◽

G Protein ◽

G Protein Signaling ◽

Protein Signaling ◽

Altered Expression ◽

And Function

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Distinct cortical and striatal actions of a β-arrestin–biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1614347113 ◽

2016 ◽

Vol 113 (50) ◽

pp. E8178-E8186 ◽

Cited By ~ 67

Author(s):

Nikhil M. Urs ◽

Steven M. Gee ◽

Thomas F. Pack ◽

John D. McCorvy ◽

Tama Evron ◽

...

Keyword(s):

G Protein ◽

Dopamine D2 Receptor ◽

D2 Receptor ◽

G Protein Signaling ◽

Protein Signaling ◽

Partial Agonists ◽

Elevated Expression ◽

Fast Spiking ◽

Cortical Dysfunction ◽

G Protein Coupled

The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Using neuron-specific βarr2-KO mice, we show that the antipsychotic-like effects of a βarr2-biased D2R ligand are driven through both striatal antagonism and cortical agonism of D2R-βarr2 signaling. Furthermore, βarr2-biased D2R agonism enhances firing of cortical fast-spiking interneurons. This enhanced cortical agonism of the biased ligand can be attributed to a lack of G-protein signaling and elevated expression of βarr2 and G protein-coupled receptor (GPCR) kinase 2 in the cortex versus the striatum. Therefore, we propose that βarr2-biased D2R ligands that exert region-selective actions could provide a path to develop more effective antipsychotic therapies.

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