BackgroundGastric cancer is one of the most common malignant tumors. Cyclin G2 has been shown to be associated with the development of multiple types of tumors, but its underlying mechanisms in gastric tumors is not well-understood. The aim of this study is to investigate the role and the underlying mechanisms of cyclin G2 on Wnt/β-catenin signaling in gastric cancer.MethodsReal-time PCR, immunohistochemistry and in silico assay were used to determine the expression of cyclin G2 in gastric cancer. TCGA datasets were used to evaluate the association between cyclin G2 expression and the prognostic landscape of gastric cancers. The effects of ectopic and endogenous cyclin G2 on the proliferation and migration of gastric cancer cells were assessed using the MTS assay, colony formation assay, cell cycle assay, wound healing assay and transwell assay. Moreover, a xenograft model and a metastasis model of nude mice was used to determine the influence of cyclin G2 on gastric tumor growth and migration in vivo. The effects of cyclin G2 expression on Wnt/β-catenin signaling were explored using a TOPFlash luciferase reporter assay, and the molecular mechanisms involved were investigated using immunoblots assay, yeast two-hybrid screening, immunoprecipitation and Duolink in situ PLA. Ccng2−/− mice were generated to further confirm the inhibitory effect of cyclin G2 on Wnt/β-catenin signaling in vivo. Furthermore, GSK-3β inhibitors were utilized to explore the role of Wnt/β-catenin signaling in the suppression effect of cyclin G2 on gastric cancer cell proliferation and migration.ResultsWe found that cyclin G2 levels were decreased in gastric cancer tissues and were associated with tumor size, migration and poor differentiation status. Moreover, overexpression of cyclin G2 attenuated tumor growth and metastasis both in vitro and in vivo. Dpr1 was identified as a cyclin G2-interacting protein which was required for the cyclin G2-mediated inhibition of β-catenin expression. Mechanically, cyclin G2 impacted the activity of CKI to phosphorylate Dpr1, which has been proved to be a protein that acts as a suppressor of Wnt/β-catenin signaling when unphosphorylated. Furthermore, GSK-3β inhibitors abolished the cyclin G2-induced suppression of cell proliferation and migration.ConclusionsThis study demonstrates that cyclin G2 suppresses Wnt/β-catenin signaling and inhibits gastric cancer cell growth and migration through Dapper1.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0973-2) contains supplementary material, which is available to authorized users.

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PSD (postsynaptic density)-95, a scaffold protein that tethers NMDA (N-methyl-D-aspartate) receptors to signal molecules, is implicated in pathological events resulting from excitotoxicity. The present study demonstrates that brain ischaemia and reperfusion increase the tyrosine phosphorylation of PSD-95 in the rat hippocampus. PP2, a specific inhibitor of SrcPTKs (Src family protein tyrosine kinases), prevents the ischaemia-induced increases not only in the tyrosine phosphorylation of PSD-95, but also in the interaction between PSD-95 and Src kinases. PSD-95 is phosphorylated either by purified Src/Fyn kinases in vitro or by co-expression of constitutively active Src/Fyn in COS7 cells. The results suggest that SrcPTKs are involved in PSD-95 phosphorylation. The single Tyr(523) mutation to phenylalanine (Y523F) reduces the Src/Fyn-mediated phosphorylation of PSD-95 in COS7 cells and in vitro. As shown with a rabbit polyclonal antibody against phospho-PSD-95 (Tyr(523)), Tyr(523) phosphorylation is responsible for the increased tyrosine phosphorylation of PSD-95 induced by ischaemia in the rat hippocampus. In cultured hippocampal neurons, overexpression of PSD-95 Y523F, but not PSD-95 Y533F, abolishes the facilitating effect of PSD-95 on the glutamate- or NMDA-mediated currents, implying that PSD-95 Tyr(523) phosphorylation contributes to the post-ischaemic over-activation of NMDA receptors. Thus the present study reveals an additional mechanism for the regulation of PSD-95 by tyrosine phosphorylation. This mechanism may be of pathological significance since it is associated with excitotoxicity in the ischaemic brain.

Cyclin G2 has been identified as a tumour suppressor in several cancers. However, its regulatory roles and underlying mechanisms in tumours are still unknown. In this study, we demonstrated that cyclin G2 was expressed at low levels in glioma, which was as a poor prognostic factor for this disease. We also found that, cyclin G2 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that cyclin G2 plays a tumour suppressive role in glioma. Mechanistically, cyclin G2 could negatively regulate tyrosine-10 phosphorylation of a critical glycolytic enzyme, lactate dehydrogenase A, through direct interaction. Taken together, these results indicate that cyclin G2 acts as a tumour suppressor in glioma by repressing glycolysis and tumour progression through its interaction with LDHA.

Fyn mediates PSD-95Y523 phosphorylation, which may be responsible for the excitotoxic signal cascades and neuronal apoptosis in brain ischemia and Aβ neurotoxicity. Fyn is a potential therapeutic target for the treatment of ischemic stroke and AD.

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Aim: To observe the effects of Ginkgo biloba extract (EGb) on the hypertrophy of mesangial cells and the accumulation of extracellular matrix (ECM) in mesangial cells. Methods: Cultured mesangial cells were allotted into 7 groups: normal group, solvent control group, high glucose group, low dose of EGb group, moderate dose of EGb group, high dose of EGb group, and captopril group. Activities of cell antioxidases, S phase percentage and G0/G1 phase percentage, collagen IV and laminin, Smad2/3 and Smad7, TGF‐β1 mRNA were measured by different methods. Results: For EGb‐treated groups, when compared with high glucose group, the cell percentage of S phase was raised and the percentage of G0/G1 was lowered. The intensity of oxidative stress was weakened. The expression of Smad2/3 was greatly decreased and Smad7 was increased. Collagen IV, laminin and TGF‐β1 mRNA were also reduced. Conclusion: EGb can suppress cell hypertrophy and the accumulation of ECM in rat mesangial cells, which means it could play a vital role in the delay of glomerulosclerosis in diabetic nephropathy.