Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) accounts for approximately 85-90% of all liver cancer cases and has poor relapse-free survival. There are many gene expression studies that have been performed to elucidate the genetic landscape and driver pathways leading to HCC. However, existing studies have been limited by the sample size and thus the pathogenesis of HCC is still unclear. In this study, we performed an integrated characterization using four independent datasets including 320 HCC samples and 270 normal liver tissues to identify the candidate genes and pathways in the progression of HCC. A total of 89 consistent differentially expression genes (DEGs) were identified. Gene-set enrichment analysis revealed that these genes were significantly enriched for cellular response to zinc ion in biological process group, collagen trimer in the cellular component group, extracellular matrix (ECM) structural constituent conferring tensile strength in the molecular function group, protein digestion and absorption, mineral absorption and ECM-receptor interaction. Network system biology based on the protein-protein interaction (PPI) network was also performed to identify the most connected and important genes based on our DEGs. The top five hub genes including osteopontin (SPP1), Collagen alpha-2(I) chain (COL1A2), Insulin-like growth factor I (IGF1), lipoprotein A (LPA), and Galectin-3 (LGALS3) were identified. Western blot and immunohistochemistry analysis were employed to verify the differential protein expression of hub genes in HCC patients. More importantly, we identified that these five hub genes were significantly associated with poor disease-free survival and overall survival. In summary, we have identified a potential clinical significance of these genes as prognostic biomarkers for HCC patients who would benefit from experimental approaches to obtain optimal outcome.
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PMID:Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Pathways Associated With Clinical Outcome in Hepatocellular Carcinoma. 3284 13

Background We previously reported that osteopontin plays an essential role in accelerating both reparative fibrosis and clearance of dead cells (efferocytosis) during tissue repair after myocardial infarction (MI) and galectin-3hiCD206+ macrophages is the main source of osteopontin in post-MI heart. Interleukin-10- STAT3 (signal transducer and activator of transcription 3)-galectin-3 axis is essential for Spp1 (encoding osteopontin) transcriptional activation in cardiac macrophages after MI. Here, we investigated the more detailed mechanism responsible for functional maturation of osteopontin-producing macrophages. Methods and Results In post-MI hearts, Spp1 transcriptional activation occurred almost exclusively in MerTK (Mer tyrosine kinase)+ galectin-3hi macrophages. The induction of MerTK on galectin-3hi macrophages is essential for their functional maturation including efferocytosis and Spp1 transcriptional activity. MerTK+galectin-3hi macrophages showed a strong activation of both STAT3 and ERK (extracellular signal-regulated kinase). STAT3 inhibition suppressed the differentiation of osteopontin-producing MerTK+galectin-3hi macrophages, however, STAT3 activation was insufficient at inducing Spp1 transcriptional activity. ERK inhibition suppressed Spp1 transcriptional activation without affecting MerTK or galectin-3 expression. Concomitant activation of ERK is required for transcriptional activation of Spp1. In Il-10 knockout enhanced green fluorescent protein-Spp1 knock-in mice subjected to MI, osteopontin-producing macrophages decreased but did not disappear entirely. Interleukin-10 and macrophage colony-stimulating factor synergistically activated STAT3 and ERK and promoted the differentiation of osteopontin-producing MerTK+galectin-3hi macrophages in bone marrow-derived macrophages. Coadministration of anti-interleukin-10 plus anti-macrophage colony-stimulating factor antibodies substantially reduced the number of osteopontin-producing macrophages by more than anti-interleukin-10 antibody alone in post-MI hearts. Conclusions Interleukin-10 and macrophage colony-stimulating factor act synergistically to activate STAT3 and ERK in cardiac macrophages, which in turn upregulate the expression of galectin-3 and MerTK, leading to the functional maturation of osteopontin-producing macrophages.
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PMID:MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin-Producing Reparative Macrophages After Myocardial Infarction. 3286 99


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