2016
DOI: 10.18632/genesandcancer.105
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Epigenetically silenced GNG4 inhibits SDF1α/CXCR4 signaling in mesenchymal glioblastoma

Abstract: The most common and aggressive form of primary brain tumor in adults is glioblastoma (GBM). From the global DNA methylation profiling study, previously published from our laboratory, we identified Guanine Nucleotide binding-protein Gamma subunit 4 (GNG4) to be one of the most hyper methylated and down regulated genes in GBM. GBM derived cell lines showed reduced GNG4 transcript levels, which could be reversed by methylation inhibitor treatment. Bisulphite sequencing confirmed the methylation status in glioblas… Show more

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Cited by 41 publications
(44 citation statements)
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References 50 publications
(57 reference statements)
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“…GNG4 is a member of the gamma subunit of the G protein family, regulates the interaction between the muscarinic receptor and voltage-sensitive calcium channels (Kalyanaraman et al, 1998), and is a putative tumor suppressor. In RCC, GNG4 is a target gene of the tumor suppressor von Hippel-Lindau gene (Maina et al, 2005), and in GBM, GNG4 is one of the most hypermethylated and down regulated genes and has tumor suppressive functions through regulation of the CXCR4/SDF1a signaling axis (Pal et al, 2016). TNFAIP1 is induced by tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) and has roles in DNA synthesis, DNA repair, and apoptosis (Wolf et al, 1992).…”
Section: Discussionmentioning
confidence: 99%
“…GNG4 is a member of the gamma subunit of the G protein family, regulates the interaction between the muscarinic receptor and voltage-sensitive calcium channels (Kalyanaraman et al, 1998), and is a putative tumor suppressor. In RCC, GNG4 is a target gene of the tumor suppressor von Hippel-Lindau gene (Maina et al, 2005), and in GBM, GNG4 is one of the most hypermethylated and down regulated genes and has tumor suppressive functions through regulation of the CXCR4/SDF1a signaling axis (Pal et al, 2016). TNFAIP1 is induced by tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) and has roles in DNA synthesis, DNA repair, and apoptosis (Wolf et al, 1992).…”
Section: Discussionmentioning
confidence: 99%
“…Mechanistically, forced expression of GNG4 inhibits GBM cell migration by decreasing the activation of ERK and JNK via stromal cell-derived factor 1α/C-X-C motif chemokine receptor 4-dependent chemokine signaling ( 31 ). Depletion of PSMC3-interacting protein represses cell viability and xenograft tumorigenesis of hepatocellular carcinoma (HCC) cells via upregulation of GNG4 ( 32 ).…”
Section: Discussionmentioning
confidence: 99%
“…MiR-181b promotes cell proliferation and reduces apoptosis by downregulating ADCY9 expression in cervical cancer cells [ 45 ]. GNG4 is a hypermethylated/low-expression gene identified in glioblastoma, and overexpression of GNG4 inhibited the proliferation of glioblastoma cells [ 46 ]. NPY is a 36-amino acid peptide that acts via G-protein-coupled receptors (Y1–Y6).…”
Section: Discussionmentioning
confidence: 99%