ABSTRACT
MicroRNAs (miRNA) are considered to be potential therapeutic targets for the treatment of various cardiovascular diseases (CVDs). To understand the underlying mechanism of miRNAs and target genes associated with CVD, deep sequencing of blood samples from three patients with CVD and three controls was performed using the Illumina HiSeq 2000 system. The results of the present study revealed that 65 abnormal hsamiRNAs targeted 2,784 putative genes in patients with CVD; 59 upregulated miRNAs targeted 2,401 genes and six downregulated miRNAs targeted 383 genes. In addition, a total of 49 Gene Ontology (GO) biological processes and were enriched, and the target genes of downregulated miRNAs were enriched in 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of these pathways are responsible for lipid and glycan metabolism. In particular, three downregulated miRNAs, hsamiR1268b, hsamiR1273d, hsamiR31875p, were involved in alinolenic acid metabolism. The target genes of upregulated miRNAs were enriched in 15 KEGG pathways, mainly in the 'neurodegenerative diseases and cancers' class. In the present study five novel upregulated miRNAs, including m04995p, m09705p, m10425p, m10615p and m19535p, and a downregulated miRNA, novelm16275p, were identified in patients with CVD. Novelm16275p was demonstrated to target 146 human genes. Additionally, Novelm10615p targeted four genes, including fumarylacetoacetate hydrolase domain containing 2A, potassium voltagegated channel, Shawrelated subfamily, member 4, coiledcoil domain containing 85C and solute carrier family 35 member E3 (SLC35E3). The GO term, 'carbohydrate derivative transport involving in biological process', was associated with SLC35E3. Novelm10615p in patients with CVD may repress the expression levels of SLC35E3, a member of the nucleoside sugar transporter subfamily E, which is known to cause defective glycolconjugation in the Golgi complex and/or the endoplasmic reticulum. Further investigation is required to understand the underlying mechanisms of the novel miRNAs. Novelm10615p may serve as a marker for prognosis or a potential target for the treatment of CVD.
Subject(s)
Cardiovascular Diseases/genetics , Gene Expression Regulation , MicroRNAs/genetics , RNA Interference , Computational Biology/methods , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Humans , Molecular Sequence Annotation , Sequence Analysis, RNAABSTRACT
OBJECTIVE: To investigate the significance of beta-adrenergic receptor 2 (beta2-AR) and vascular endothelial growth factor-2 (VEGFR-2) in the occurrence and development of infantile hemangioma through detecting the expression of beta2-AR and VEGFR-2 in the different stages of infantile hemangiomas. METHODS: According to the Mulliken's classification standard, we classified the specimens as proliferating group (32 cases), involuting group (17 cases) and involuted group (11 cases). Normal skin tissue surrounding the hemangioma from 7 cases were chosen as control group. The expression of beta2-AR and VEGFR-2 was detected by immunohistochemical technique in proliferating hemangioma, involuting hemangioma, involuted hemangioma. The mean optical density was measured by image analysis system (Image Pro Plus 6.0) and SPSS 16.0 software was applied for statistical analysis. RESULTS: The expression of beta2-AR and VEGFR-2 was strongly positive in proliferating hemangioma, while positive in involuting hemangioma and weakly positive in the involuted stage. The mean optical density of each phase was 0.064 751 2 +/- 0.012 747, 0.031 6017 +/- 0.006 848,0.011 869 8 +/- 0.039 349 for beta2-AR, and 0.068 940 9 +/- 0.029 274, 0.028 445 5 +/- 0.006 396, 0.011 184 1 +/- 0.004 198 for VEGFR-2. The differences between different stages had a statistically significance (P < 0.05). Correlation analysis on the mean optical density between beta2-AR and VEGFR-2 had a statistically significance (P < 0. 05). CONCLUSIONS: Beta2-AR and VEGFR-2 may be involved in the occurrence and development of infantile hemangioma.