Prediction and analysis of bioinformatics of novel tumor suppressive target SLC33A1 gene / 中国生物制品学杂志

@#Objective To predict and analyze the physical and chemical properties,structure,function,protein interaction and homology of SLC33A1 gene based on bioinformatics so as to provide a reference for further study on the function of SLC33A1.Methods A variety of bioinformatics tools were used to predict the physical and chemical properties,hydrophilicity,hydrophobicity,signal peptide structure,transmembrane structure,subcellular localization,three dimensional spatial structure,post-translational modification sites and protein-protein interaction of SLC33A1.Results SLC33A1 was a neutral,stable and hydrophobic protein without signal peptide sequence,which was mainly distributed in cell membrane and membrane structural organelle,with a probability of 13. 0% in vesicle membrane. There were 11 transmembrane domains,6 extracellular domains and 6 intracellular domains in SLC33A1 sequence. The tertiary structure of SLC33A1 was elastic and stable,which had 2 N-glycosylation sites,2 O-glycosylation sites and 13 potential protein phosphorylation sites. SLC33A1 interacted with 7 proteins such as ATM with high confidence,which was mainly involved in the negative regulation of inositol-requiring enyzme 1(IRE1)-mediated unfolded protein response,the respon-ses of glycosphingolipid,sialylation and cells to γ ray as well as the negative regulation of endoplasmic reticulum stress response.Conclusion The nature and function of SLC33A1 were investigated by various software,which provided theoretical references and ideas for further research on new anticancer targets in the future.

Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug.

Dasatinib is a multi-target protein tyrosine kinase inhibitor. Due to its potent inhibition of Src, Abl, the platelet-derived growth factor receptor (PDGFR) family kinases, and other oncogenic kinases, it has been investigated as a targeted therapy for a broad spectrum of cancer types. However, its efficacy has not been significantly extended beyond leukemia. The mechanism of resistance to dasatinib in a wide array of cancers is not clear. In the present study, we investigated the effect of dasatinib on hepatocellular carcinoma cell growth and explored the underlying mechanisms. Our results showed that dasatinib potently inhibited the proliferation of SNU-449 cells, but not that of other cell lines, such as SK-Hep-1, even though it inhibited the phosphorylation of Src on both negative and positive regulation sites in all these cells. Dasatinib activated the phosphoinositide-dependent protein kinase1 (PDK1)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in SK-Hep-1 cells, but not in SNU-449 cells. Blocking the Akt/mTOR signaling pathway strongly promoted the efficacy of dasatinib in SK-Hep-1 cells. In SNU-449 cells, dasatinib promoted apoptosis and the cleavage of caspase-3 and caspase-7, induced cell cycle arrest in the G1 phase, and inhibited the expression of Cyclin-dependent kinase (CDK4)/6/CyclinD1 complex. These findings demonstrate that dasatinib exerts its anti-proliferative effect on hepatocellular cell proliferation by blocking the Src family kinases; however, it causes Akt activation, which compromises dasatinib as an anti-cancer drug.

Higher postoperative plasma EV PD-L1 predicts poor survival in patients with gastric cancer.

BACKGROUND: The satisfactory prognostic indicator of gastric cancer (GC) patients after surgery is still lacking. Perioperative plasma extracellular vesicular programmed cell death ligand-1 (ePD-L1) has been demonstrated as a potential prognosis biomarker in many types of cancers. The prognostic value of postoperative plasma ePD-L1 has not been characterized. METHODS: We evaluated the prognostic value of preoperative, postoperative and change in plasma ePD-L1, as well as plasma soluble PD-L1, in short-term survival of GC patients after surgery. The Kaplan-Meier survival model and Cox proportional hazards models for both univariate and multivariate analyzes were used. And the comparison between postoperative ePD-L1 and conventional serum biomarkers (carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4) in prognostic of GC patients was made. RESULTS: The prognostic value of postoperative ePD-L1 is superior to that of preoperative ePD-L1 on GC patients after resection, and also superior to that of conventional serum biomarkers (CEA, CA19-9 and CA72-4). The levels of postoperative ePD-L1 and ePD-L1 change are independent prognostic factors for overall survival and recurrence free survival of GC patients. High plasma level of postoperative ePD-L1 correlates significantly with poor survival, while high change in ePD-L1 level brings the significant survival benefit. CONCLUSIONS: The level of plasma postoperative ePD-L1 could be considered as a candidate prognostic biomarker of GC patients after resection.

Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl­2 pathway.

Diffuse large B­cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism. The results demonstrated that chidamide induced the death of these cells in a concentration­(0­30 µmol/l) and time­dependent (24­72 h) manner, as determined using the Cell Counting Kit­8 cell viability assay. Moreover, chidamide promoted cellular apoptosis, which was identified via flow cytometry and western blot analysis, with an increase in cleaved caspase­3 expression and a decrease in Bcl­2 expression. Chidamide treatment also decreased the expression level of STAT3 and its phosphorylation, which was accompanied by the downregulation of a class­I histone deacetylase (HDAC) inhibitor, chidamide. Collectively, these data suggested that chidamide can be a potent therapeutic agent to treat DLBCL by inducing the apoptotic death of DLBCL cells by inhibiting the HDACs/STAT3/Bcl­2 pathway.