Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high-density micromass culture has been widely applied to study chondrocyte cell physiology and pathophysiological mechanisms. Since an integrated image has not been established so far, we analyzed the phenotypic alterations of human articular chondrocytes in this model on the broad molecular level. Freshly isolated chondrocytes were assembled as micromasses and maintained up to 6 weeks in medium containing human serum. Formation of cartilaginous extracellular matrix (ECM) was evaluated by histological and immunohistochemical staining. At 0, 3 and 6 weeks, chondrocyte micromasses were subjected to gene expression analysis using oligonucleotide microarrays and real-time RT-PCR. Micromasses developed a cartilaginous ECM rich in proteoglycans and type II collagen. On gene expression level, time-dependent expression patterns was observed. The induction of genes associated with cartilage-specific ECM (COL2A1 and COL11A1) and developmental signaling (GDF5, GDF10, ID1, ID4 and FGFR1-3) indicated redifferentiation within the first 3 weeks. The repression of genes related to stress response (HSPA1A and HSPA4), apoptotic events (HYOU1, NFKBIA and TRAF1), and degradation (MMP1, MMP10 and MMP12) suggested a recovery of chondrocytes. Constant expression of other chondrogenic (ACAN, FN1 and MGP) and hypertrophic markers (COL10A1, ALPL, PTHR1 and PTHR2) indicated a pattern of phenotypic maintenance. Simultaneously, the expression of chondrogenic growth (BMP6, TGFA, FGF1 and FGF2) and transcription factors (SOX9, EGR1, HES1 and TGIF1), and other cartilage ECM-related genes (COMP and PRG4) was consistently repressed and expression of collagens related to dedifferentiation (COL1A1 and COL3A1) was steadily induced indicating a progressing loss of cartilage phenotype. Likewise, a steady increase of genes associated with proliferation (GAS6, SERPINF1, VEGFB and VEGFC) and apoptosis (DRAM, DPAK1, HSPB, GPX1, NGFRAP1 and TIA1) was observed. Sequence and interplay of identified expression patterns suggest that chondrocyte micromass cultures maintain a differentiated phenotype up to 3 weeks in vitro and might be useful for studying chondrocyte biology, pathophysiology and differentiation. Cultivation longer than 6 weeks leads to progressing dedifferentiation of chondrocytes that should be considered on long-term evaluations.
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PMID:Gene expression profiling of primary human articular chondrocytes in high-density micromasses reveals patterns of recovery, maintenance, re- and dedifferentiation. 2043 12

Papillary thyroid cancer (PTC) is the most prevalent histological type among thyroid cancers, and some patients are at a high risk for recurrent disease or even death. Identification for the potential biomarkers of PTC may contribute to early discovery of recurrence and treatment. In The Cancer Genome Atlas (TCGA) database, we obtained the information of RNA sequence data and clinical characteristics of PTC. Weighted gene co-expression network analysis (WGCNA) was performed to construct gene co-expression networks and investigate the relationship between modules and clinical traits. Finally, we constructed 16 co-expression modules in 10,428 genes, and three key modules (darkturquoise, lightyellow, and red) associated with tumor N grade were identified. The results of functional annotation indicated that the darkturquoise module was primarily enriched in the regulation of the extracellular matrix (ECM), collagen metabolism, and cell adhesion, the lightyellow module was primarily enriched in the mitochondrial function regulation and energy synthesis, and the red module was primarily enriched in the process of cell junction, apoptosis, and inflammatory response, suggesting their significant role in the progression of PTC. In addition, the hub genes in the three modules were identified and screened for differentially expressed genes (DEGs). Relapse-free survival analyses found that 11 genes (KCNQ3, MET, FN1, ITGA3, RUNX1, ITGA2, PERP, GCSH, FAAH, NGFRAP1, and HSPA5) may play a pivotal role in PTC relapse. In general, our research revealed the key co-expression modules and identified several prognostic biomarkers, which provides some new insights into the lymph node metastasis of PTC.
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PMID:Identification of gene co-expression modules and hub genes associated with lymph node metastasis of papillary thyroid cancer. 3133 12