Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that HLA-DR is a potent inducer of thrombin generation. Human colorectal cells (GEO, WiDr, DLD-1, and MIP) that lack the constitutive expression of HLA-DR cause platelet aggregation through a thrombin-dependent mechanism. Treatment with recombinant human gamma-interferon induced the expression of HLA-DR in the GEO, WiDr, and DLD-1 cells, whereas the MIP cell line remained HLA-DR negative. The concurrent analysis of tumor cell/platelet interaction after gamma-interferon treatment showed a decrease in platelet proaggregating activity of either the responsive GEO (highly expressing HLA-DR) or the unresponsive MIP (HLA-DR negative) cells. Furthermore, the DLD-1 (moderately expressing HLA-DR) cells showed an increase of proaggregating activity after gamma-interferon treatment, whereas WiDr (highly expressing HLA-DR) cells did not modify their activity. These results suggest a lack of a role of HLA-DR in the in vitro platelet proaggregating activity of human colorectal tumor cells.
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PMID:Evaluation of the potential role of class II histocompatibility antigen HLA-DR in platelet/tumor cell interaction. 830 20

Gastric cancer (GC) is a malignant tumor that affects individuals worldwide, and miRNA and mRNA are closely connected to this disease. However, it is still unclear how these molecules affect GC and whether their effects are associated with circRNA in GC patients. Therefore, we obtained the miRNA, mRNA and circRNA expression profiles of GC patients from the GEO database. For comparison, shared miRNAs and mRNAs from the results of microarrays were annotated by gene ontology (GO) and pathway analysis. We also identified mRNAs that were targeted by miRNA through TargetScan 7.2 and circRNAs that were targeted by miRNA through CircInteractome. A comprehensive analysis of the microarray results revealed 72 shared miRNAs, and the expression profiles of 6 miRNAs were significantly different between the tumor and control groups (the absolute value of fold change>2, P<0.05). Hsa-miR-1, hsa-miR-142-3p, hsa-miR-95, hsa-miR-133a and hsa-miR-181d were upregulated in GC, whereas hsa-miR-375 was downregulated. The analysis results also revealed 1201 shared mRNAs and 27 mRNAs, respectively, by microarray and TargetScan. Pathway analysis demonstrated that the Glypican pathway, Proteoglycan syndecan-mediated signalling events, Glypican 1 network and PAR1-mediated thrombin signalling events play important roles. GO analysis revealed significant enrichment in the three terms cellular component, molecular function and biological process, suggesting that organelles, enzyme binding, RNA-binding and nitrogen metabolism may have a strong relationship in GC. The increase in PAX6 in GC may be related to hsa-miR-375. Three circRNAs, hsa_circ_0001658, hsa_circ_0004928 and hsa_circ_0000376, were then found to be significantly differentially expressed between GC and normal tissues (the absolute value of fold change>2, P<0.05). In conclusion, the circ0001658/circ0004928/circ0000376-miR-375-PAX6 axis may represent a new regulatory network that should be further investigated, and the results of this study provide a better understanding of GC.
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PMID:miRNA and mRNA expression profiles in gastric cancer patients and the relationship with circRNA. 3130 99

Platelets are derived from megakaryocytes and play an important role in blood coagulation. By using high throughput sequencing, we have found that the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is abundant in platelets (GEO ID: 200097348). However, little is known about its role in regulating megakaryocyte differentiation and platelet activity. This study aims to clarify the effect of NEAT1 on MEG-01 differentiation and platelet-like particle (PLP) activity. NEAT1 in MEG-01 cells was knocked down by siRNA transfection. The adhesion of MEG-01 and PLP to collagen-coated coverslips was observed under a fluorescence microscope. Flow cytometry was used to investigate cell apoptosis, cell cycle, the levels of D41/CD42b on MEG-01 cells and CD62P on PLPs. Quantitative real-time polymerase chain reaction was used to detect NEAT1 and IL-8 expression levels. Western blot was used to measure the protein levels of Bcl-2, Bax, cleaved caspase-3, and IL-8. RNA-binding protein immunoprecipitation was used to detect the interaction of NEAT1 and splicing factor proline/glutamine-rich (SFPQ). Results showed that NEAT1 knockdown decreased the adhesion ability of thrombin-stimulated MEG-01 and PLP. The expression of CD62P on PLPs and CD41/CD42b on MEG-01 cells was inhibited by NEAT1 knockdown. In addition, NEAT1 knockdown inhibited cell apoptosis with increased Bcl2/Bax ratio and decreased cleaved caspase-3, and reduced the percentage of cells in the G0/G1 phase. Meanwhile, NEAT1 knockdown inhibited the expression of IL-8. A strong interaction of NEAT1 and SFPQ, a transcriptional repressor of IL-8, was identified. NEAT1 knockdown reduced the interaction between SFPQ and NEAT1.The results suggest that lncRNA NEAT1 knockdown decreases MEG-01 differentiation, PLP activity, and IL-8 level. The results also indicate that the regulation of NEAT1 on IL-8 may be realized via a direct interaction between NEAT1 and SFPQ.
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PMID:Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity. 3319 74