Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients. Interestingly, putative CCCTC-binding factor (CTCF) regulatory elements were identified within the promoters of these ECM-related genes and were confirmed by chromatin immunoprecipitation sequencing (ChIP-Seq). CTCF binding sites also overlapped with histone activation markers, indicating direct regulation. In addition, CTCF was also correlated with the Wnt signaling pathway. A comparison of human GC cell lines with high or low expression of ECM-related genes revealed different levels of tumor aggressiveness, suggesting the cancer development-promoting functions of ECM-related genes. Furthermore, CTCF regulated COL1A1 and COLA31 expression in vitro. Silencing CTCF or COL1A1/COL1A3 markedly inhibited cell growth and migration in the metastatic GC cell line BGC823. Collectively, this ECM-related 7-gene signature provides a novel insight for survival prediction among GC patients. The zinc finger protein CTCF regulates ECM-related genes, thereby promoting GC cell growth and migration.
AbstractmiRNAs are short nucleic acid sequences that regulate gene expression and are important biomarkers for disease diagnostics. In this Review, we overview the biogenesis and functions of miRNAs. The recent progress of biomarker development based on miRNAs is further discussed. In the end, we summarize the progress on miRNA detection methods towards clinical diagnostics. Although proper tools and standardized methodology in detection are still the bottlenecks for miRNA‐based diagnosis, the challenges are likely to be overcome with the development of new bioanalytical techniques. More importantly, upstream studies to elucidate mechanisms of miRNAs in target recognition and correlation with diseases will further advance the clinical use of miRNAs as biomarkers.
Selecting optimization ship form s('heme is an important content in the process of concept design of ship. Muhi-objective flJzzy decision-making model for ship form demonstration is set up ac('ording to the fuzzy pattern-recognition theory. Weight coefficients of each target of ship form scheme are determined by information entropy and individual subjective partiality. This model is use(t to select the oplimal ship form scheme,the example shows that the model is exact and the result is credible. It can provide a reference for choosing the optimization scheme of ship form.
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