ceRNA mechanism of circRNA-miRNA-mRNA in atherosclerosis

Atherosclerosis (AS) is a common cardiovascular disease and a major cause of coronary heart di-sease, cerebral infarction and peripheral vascular disease. Circular RNA (circRNA) is a class of circularly closed non-co-ding RNAs that play an important role in the formation of AS. Physiological and pathological significances of the processes such as lipid metabolism, endothelial cell damage, vascular smooth muscle cell proliferation and migration, monocyte pha-gocytosis and foam-like cell formation, and inflammatory responses are involved in the development of AS. Most circRNA adjust mRNA expression by regulating microRNAs (miRNAs). circRNA provides new ideas and targets for the diagnosis and treatment of AS.     

Functional analysis of differential microRNA expression profile in mouse fibrotic liver tissues induced by CCl4

AIM:To discover the expression profile of microRNAs (miRNAs) in mouse fibrotic liver tissues induced by carbon tetrachloride (CCl4), and to investigate the functions of these differential miRNAs based on the gene ontology (GO) analysis and KEGG Pathway analysis. METHODS:The mice were randomly divided into normal group and model group. Liver fibrosis was induced by subcutaneous injection of CCl4. miRNA expression profile of the liver tissues was assayed by a mouse miRNA microarray (Agilent 12.0). The differential expression of miRNAs between the normal and model mice was screened, and GO analysis and KEGG Pathway analysis were performed to determine the functions of these differential miRNAs. RESULTS:Thirty-nine miRNAs with differential expression were discovered in the model mice compared with the normal mice, among which 23 were up-regulated and 16 were down-regulated. GO analysis and KEGG Pathway analysis indicated that most pathological processes of liver fibrosis regulated by miRNAs included cell proliferation and activation, cell apoptosis, cell cycle, cell adhesion, inflammatory reaction, cell migration, transforming growth factor β (TGF-β) signaling pathway, Wnt signaling pathway and proteometabolism process. GO analysis revealed that the key up-regulated miRNAs were mmu-miR-322, mmu-miR-15b, mmu-miR-195, mmu-miR-200b and mmu-miR-214, and the key down-regulated miRNAs were mmu-miR-16, mmu-miR-130a, mmu-miR-101b, mmu-miR-30a and mmu-miR-30e. Analyzing the target genes screened out by GO analysis and Pathway analysis simultaneously, we found that the key up-regulated miRNAs included mmu-miR-200b, mmu-miR-322, mmu-miR-106b, mmu-miR-23a and mmu-miR-15b, and the key down-regulated miRNAs included mmu-miR-16, mmu-miR-30e, mmu-miR-30c, mmu-miR-30a and mmu-miR-130a. CONCLUSION: Differential expression of miRNAs is discovered in mouse fibrotic liver tissues induced by CCl4 compared with the normal liver tissues. Most of the pathological processes involved in liver fibrosis may be regulated by miRNA, such as cell proliferation and activation, cell adhesion and apoptosis, cell migration and differentiation, metabolism, TGF-β receptor signaling pathway and so on.     

Proctective effect of microRNA-30a on regulating beclin-1 expression in hypoxia-reoxygenated neonatal rat cardiomyocytes

AIM: To explore the potential mechanism of microRNA-30a (miR-30a) overexpression in neonatal rat cardiomyocytes during hypoxia/reoxygenation (H/R). METHODS: The miR-30a overexpression was induced in primary neonatal rat cardiomyocytes by lentivirus transfection. The cardiomyocytes were divided into 5 groups: normal group, H/R group, LV-GFP+H/R group, LV-GFP-miR-30a+H/R group and 3-methyladenine(3-MA)+H/R group. The expression level of miR-30a after lentivirus transfection and H/R was determined by real-time PCR, while the protein levels of LC3 and Beclin-1 after H/R and lentivirus transfection were detected by Western blotting. The cardiomyocyte death after H/R were measured by TUNEL and PI staining. RESULTS: Compared with LV-GFP group, significant down-regulation of Beclin-1 protein level was observed in cardiomyocytes with miR-30a overexpression, while the protein levels of Beclin-1 and LC3 in the cardiomyocytes with miR-30a overexpression were down-regulated after H/R, and apoptosis of these cells were significantly decreased after H/R. CONCLUSION: The protein level of Beclin-1 is down-regulated in cardiomyocytes with miR-30a overexpression. Inhibition of autophagy decreases the cardiomyocyte death after H/R.     

In ovo leptin administration affects hepatic lipid metabolism and microRNA expression in newly hatched broiler chickens

Background: A leptin-like immunoreactive substance has been found in chicken eggs and has been implicated in serving as a maternal signal to program offspring growth and metabolism. In the present study, we investigated the effects of in ovo leptin administration on hatch weight, serum and hepatic concentrations of metabolites and hormones, as well as on the expression of genes involved in hepatic lipid metabolism and the predicted microRNAs (miRNAs) targeting the affected genes. To this end we injected fertile eggs with either 0.5 μg of recombinant murine leptin or vehicle (PBS) before incubation. Results: Prenatally leptin-exposed chicks showed lower hatch weight, but higher liver weight relative to the body weight, compared to the control group. In ovo leptin treatment increased the hepatic content and serum concentration of leptin in newly hatched chickens. The hepatic contents of triglycerides (TG) and total cholesterol (Tch) were decreased, whereas the serum levels of TG, Tch and apolipoprotein B (ApoB) were increased. The hepatic mRNA expression of sterol regulator element binding protein 1 (SREBP-1c), SREBP-2, hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and cholesterol 7α-hydroxylase 1 (CYP7A1) was significantly up-regulated, as was the protein content of both SREBP-1c and SREBP-2 in hepatic nuclear extracts of leptin-treated chickens. Moreover, out of 12 miRNAs targeting SREBP-1c and/or HMGCR, five were significantly up-regulated in liver of leptin-treated chicks, including gga-miR-200b and gga-miR-429, which target both SREBP-1c and HMGCR. Conclusions: These results suggest that leptin in ovo decreases hatch weight, and modifies hepatic leptin secretion and lipid metabolism in newly hatched broiler chickens, possibly via microRNA-mediated gene regulation.     

Roles of microRNAs in glioma

MicroRNAs (miRNAs) are critical regulators of gene expression. These small, non-coding RNAs are believed to regulate more than one third of protein-coding genes, and have been implicated in the control of many biological processes, including the biology of glioma. The functional significance in some of the miRNAs begins to emerge. This paper reviews the biogenesis of miRNAs, their roles in neuronal development and tumorigenesis of gliomas, and their contribution as tumor biomarkers. Research in this area is quickly gathering pace and is illuminating important aspects of the diseases that may ultimately lead to novel therapeutic interventions, as well as diagnostic and prognostic tools for brain tumors.     

玉米自交系X178、掖478授粉前后miRNA表达差异分析

基于HiSeq高通量测序技术并结合生物信息学方法对X178、掖478两种材料授粉前后两个时期穗已知miRNA及靶基因进行分析。结果发现,X178授粉前后差异表达miRNA有100个,分别属于21个miRNA家族;掖478授粉前后共筛选出98个有差异的miRNA,分别属于22个miRNA家族。利用miRNA与靶基因mRNA负调控关系初步确定授粉前后miRNA可能调控的mRNA靶点,建立miRNA-靶mRNA一一对应关系。结果表明,X178中上调表达的13个miRNA对应11个下调表达靶基因,下调表达的33个miRNA对应41个上调表达靶基因;掖478中上调表达的5个miRNA对应7个下调表达靶基因,下调表达的28个miRNA对应33个上调表达靶基因,其中,6个miRNA家族共靶向11种mRNA。研究结果表明,在授粉前后玉米穗中已知miRNA在不同玉米自交系中种类具有差异。