SMAD7 methylation as a novel marker in atherosclerosis.

Atherosclerosis is a complicated process comprising inflammation, accumulation of collagen matrix and aberrant DNA methylation. SMAD7 is known to play an important role in fibrosis and inflammation. In recent years, increasing research has concentrated on the connection between DNA methylation and atherosclerosis. The current study was designed to investigate methylation status of some specific gene with a focus on SMAD7 in atherosclerosis and elucidate their relationship. We found that SMAD7 expression was decreased and its promoter region was markedly methylated in atherosclerotic plaques when compared with normal artery walls. Using MALDI-TOF MS, increased DNA methylation levels of SMAD7 promoter at CpG unit 5.8.15.16 were found in peripheral blood of atherosclerosis patients relative to matched normal controls, respectively. Correlation analysis revealed that mean DNA methylation levels of SMAD7 promoter of CpG unit 5.8.15.16 were positively associated with homocysteine levels (r = 0.724, p < .001) and carotid plaque scores(r = 0.790, p < .001). SMAD7 promoter is hyper-methylated both in human atherosclerotic plaques and atherosclerosis patients, which is positively associated with homocysteine levels and carotid plaque scores. Thus, methylated SMAD7 may be a novel predicted marker and therapeutics target for atherosclerosis.

MiR-375: A prospective regulator in medullary thyroid cancer based on microarray data and bioinformatics analyses.

BACKGROUND: This research aims to investigate the prospective molecular mechanism of miR-375 in Medullary Thyroid Cancer (MTC). MATERIAL AND METHODS: The expression level of miR-375 in MTC was explored with microarray data from Gene Expression Omnibus (GEO). To gather the putative target genes of miR-375, we selected eligible datasets in GEO, in which antagomir-375 and premir-375 were transfected to provide the miR-375-related genes. Subsequently, we attained the intersection of the results of GEO microarray data and 12 online target genes prediction database as the prospective target genes. Furthermore, we conducted in silico analysis including gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways annotations and Protein-Protein Interactions (PPI) analysis to provide an overview of the function of miR-375 in MTC. Finally, data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) were used for a validation. RESULTS: Up-regulation could be confirmed with the data from GSE40807. GEO dataset GSE67742 provided 10,596 miR-375-related genes, while 12 online prediction databases showed that 3352 target genes appeared no less than four times. Finally, the intersection of the two groups of genes included 1132 prospective targets. In aspect of functional annotation, negative regulation of transcription from RNA polymerase II promoter (P=9.83E-06), golgi membrane (P=9.98E-05) and pathway of protein binding (P=3.63E-07) were highlighted as the most enriched terms with GO analysis. With regards to PPI network, 162 hub genes that interacted with no less than 10 other different genes was visualized, among which PI3K/Akt signaling pathway was the most enriched pathway as assessed by KEGG. Furthermore, two genes (JAK2 and NGFR) in PI3K/Akt signaling pathway showed down-regulated patterns in both mRNA and protein levels. CONCLUSION: The higher expression level of miR-375 might play a pivotal role in the tumorigenesis of MTC via targeting multiple key pathways, especially PI3K/Akt pathway. However, the exact molecular mechanism of miR-375 needs to be verified with in-depth investigation in the future.