Silencing of lncRNA ZFAS1 inhibits malignancies by blocking Wnt/β-catenin signaling in gastric cancer cells

Gastric cancer is a common malignancy with high mortality. Long noncoding RNA (lncRNA) zinc finger antisense (ZFAS)1 is upregulated in gastric cancer specimens compared with the para-carcinoma tissues. The silencing of ZFAS1 inhibited the growth, proliferation, cell cycle progress, migration, invasion and epithelial-mesenchymal transition (EMT), and enhanced the sensitivity to cis-platinum or paclitaxel in SGC7901 cells, as evidenced by the expression changes of proliferating cell nuclear antigen, Cyclin D1, Cyclin E, Cyclin B1, E-cadherin, N-cadherin, vimentin, matrix metalloproteinase (MMP)-2 and MMP-14. The ZFAS1 also activated the Wnt/β-catenin signaling. Subsequently, the ZFAS1 knockdown-induced the inhibition of migration, invasion, EMT and resistance to chemotherapeutic reagens was reversed by the overexpression of β-catenin. In summary, the silencing of ZFAS1 inhibited the growth, proliferation, cell cycle progress, migration, invasion, EMT and chemotherapeutic tolerance by blocking the Wnt/β-catenin signaling in gastric cancer cells.     

Anti-IL-23 exerted protective effects on cerebral ischemia–reperfusion injury through JAK2/STAT3 signaling pathway

Molecular Biology Reports - Ischemia–reperfusion frequently occurs in ischemic cerebral vascular disease, during which the inflammatory signaling plays essential roles. The aim of this study...     

Genistein-3′-sodium sulfonate ameliorates cerebral ischemia injuries by blocking neuroinflammation through the α7nAChR-JAK2/STAT3 signaling pathway in rats

BackgroundNeuroinflammation plays a pivotal role in the acute progression of cerebral ischemia/reperfusion injury (I/RI). We previously reported that genistein-3′-sodium sulfonate (GSS), a derivative from the extract of the phytoestrogen genistein (Gen), protects cortical neurons against focal cerebral ischemia. However, the molecular mechanism underlying the neuroprotective effects exerted by GSS remains unclear.PurposeThe present study focused on the anti-inflammatory effects of GSS following I/RI in rats.Study designRandomized controlled trial.MethodsThe tMCAO rat model and LPS-stimulated BV2 in vitro model were used. Longa's scare was used to observe neurological function. TTC staining and Nissl staining were used to evaluate brain injury. ELISA, qRT-PCR, Western blotting and immunofluorescent staining methods were used to detect cytokine concentration, mRNA level, protein expression and location.ResultsGSS treatment improves neurological function, reduces the volume of cerebral infarction, attenuates proinflammatory cytokines and inactivates the phosphorylation of JAK2 and STAT3 in I/RI rats. Furthermore, GSS increased the expression of α7nAChR. More importantly, the neuroprotective, anti-inflammatory and inhibiting JAK2/STAT3 signaling pathway effects of GSS were counteracted in the presence of alpha-bungarotoxin (α-BTX), an α7nAChR inhibitor, suggesting that α7nAChR is a potential target associated with the anti-inflammatory effects of GSS in the I/RI rats. GSS also inhibited BV2 cells from releasing IL-1β via the α7nAChR pathway after LPS stimulation.ConclusionGSS protects against cerebral I/RI through the expression of α7nAChR and inhibition of the JAK2/STAT3 pathway. Our findings provide evidence for the role of the cholinergic anti-inflammatory pathway in neuroinflammation and uncover a potential novel mechanism for GSS treatment in ischemic stroke. The downstream signals of GSS, α7nAChR- JAK2/STAT3 could also be potential targets for the treatment of I/RI.     

NOK通过JAK2依赖性方式激活STAT3信号通路

NOK能激活包含JAK-STAT信号通路在内的多种促细胞有丝分裂信号通路.研究发现,在人胚肾细胞(HEK293T)中,NOK与STAT3具有直接的相互作用.进一步的实验表明,NOK能同STAT3蛋白除螺旋结构域及c端结构域外的其他4个结构域发生相互作用,而NOK的胞内区则介导了NOK同STAT3的相互作用.同时,免疫共沉淀实验显示,NOK能与JAK2发生相互作用.重要的是,共同表达NOK与JAK2蛋白对STAT3信号通路能产生一种非常显著的协同激活作用,但当共同表达NOK和JAK2的激酶活性缺失突变体时,并不产生这种协同激活效应.综上,实验结果显示,NOK可能同STAT3和JAK2形成一个复合物,通过JAK2依赖性方式激活STAT3信号通路.     

Helicobacter pylori promotes epithelial-to-mesenchymal transition by downregulating CK2β in gastric cancer cells

Strains of Helicobacter pylori that are positive for the oncoprotein CagA (cytotoxin-associated gene A) are associated with gastric cancer and might be related to the epithelial-to-mesenchymal transition (EMT). Casein kinase 2 (CK2) is a serine/threonine protein kinase that plays a major role in tumorigenesis through signaling pathways related to the EMT. However, the role played by the interaction between CagA and CK2 in gastric carcinogenesis is poorly understood. Although CK2α protein expression remained unchanged during H. pylori infection, we found that CK2α kinase activity was increased in gastric epithelial cells. We also found that the CK2β protein level decreased in H. pylori-infected gastric cancer cells in CagA-dependent manner and demonstrated that CagA induced CK2β degradation via HDM2 (human double minute 2; its murine equivalent is MDM2). We observed that CagA induced HDM2 protein phosphorylation and that p53 levels were decreased in H. pylori-infected gastric cancer cells. In addition, downregulation of CK2β induced AKT Ser473 phosphorylation and decreased the AKT Ser129 phosphorylation level in gastric cancer cells. We also found that the downregulation of CK2β triggered the upregulation of Snail levels in gastric cancer cells. Furthermore, our in vivo experiments and functional assays of migration and colony formation suggest that CK2β downregulation is a major factor responsible for the EMT in gastric cancer. Therefore, CK2 could be a key mediator of the EMT in H. pylori-infected gastric cancer and could serve as a molecular target for gastric cancer treatment.