AIM： TO identify the differentially expressed miRNAs and their targets in hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： Six hundred and sixty seven human miRNAs were quantitatively ...AIM： TO identify the differentially expressed miRNAs and their targets in hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： Six hundred and sixty seven human miRNAs were quantitatively analyzed by Taqman lowdensity miRNA array （TLDA） in HBV-HCC tissues. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were used to analyze the significant function and pathway of the differentially expressed miRNAs in HBV-HCC. TargetScan software was used to predict the targets of deregulated miRNAs. Western blotting and luciferase assay were performed to verify the targets of these miRNAs.RESULTS： Ten up-regulated miRNAs （miR-217, miR- 518b, miR-517c, miR-520g, miR-519a, miR-522, miR- 518e, miR-525-3p, miR-512-3p, and miR-518a-3p） and 11 down-regulated miRNAs （miR-138, miR-214, miR-214#, miR-199a-5p, miR-433, miR-511, miR-592, miR-483-3p, miR-483-5p, miR-708 and miR-1275） were identified by Taqman miRNAs array and confirmed quantitatively by reverse transcription polymerase chain reaction in HCC and adjacent non-tumor tissues. GO and KEGG pathway analysis revealed that ＂regulation of actin cytoskeleton＂ and ＂pathway in cancer＂ are most likely to play critical roles in HCC tumorigenesis. MiR- 519a and ribosomal protein S6 kinase polypeptide 3 （RPS6KA3） were predicted as the most significant can-didates by miRNA-mRNA network. In addition, cyclin D3 （CCND3） and clathrin heavy chain （CHC）, usually up-regulated in HCC tissues, were validated as the di- rect target of miR-138 and miR-199a-5p, respectively.展开更多
Multiple sclerosis(MS)is a chronic and incurable autoimmune neurodegenerative disease of the central nervous system.Although the symptoms of MS can be managed by vitamin D3 treatment alone,this condition cannot be com...Multiple sclerosis(MS)is a chronic and incurable autoimmune neurodegenerative disease of the central nervous system.Although the symptoms of MS can be managed by vitamin D3 treatment alone,this condition cannot be completely eradicated.Thus,there might be unknown factors capable of regulating the vitamin D receptor(VDR).Genome-wide analysis showed that miRNAs were associated with VDRs.We sought to determine the role and mechanism of action of miRNA-125a-5p and VDRs in a model of MS,mice with experimental autoimmune encephalomyelitis(EAE),which was induced by myelin oligodendrocyte glycoprotein 35–55 peptides.EAE mice showed decreased mean body weight but increased mean clinical scores compared with vehicle or control mice.And inflammatory infiltration was found in the lumbosacral spinal cord of EAE mice.In addition,VDR expression was significantly lower while the expression of miR-125a-5p was markedly higher in the spinal ventral horn of EAE mice than in vehicle or control mice.Importantly,activation of VDRs by paricalcitol or inhibition of miR-125a-5p by its antagomir markedly decreased the mean clinical scores in EAE mice.Interestingly,VDR and miR-125a-5p were co-localized in the same neurons of the ventral horn.More importantly,inhibition of miR-125a-5p remarkably blocked the decrease of VDRs in EAE mice.These results support a critical role for miR-125a-5p in modulating VDR activity in EAE and suggest potential novel therapeutic interventions.展开更多
基金Supported by The Key Programs of the Ministry of Science and Technology, No. 2012ZX10002009-004Shanghai Leading Academic Discipline Project (B901)Science Fund for Creative Research Groups, NSFC, China, No. 30921006
文摘AIM： TO identify the differentially expressed miRNAs and their targets in hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： Six hundred and sixty seven human miRNAs were quantitatively analyzed by Taqman lowdensity miRNA array （TLDA） in HBV-HCC tissues. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were used to analyze the significant function and pathway of the differentially expressed miRNAs in HBV-HCC. TargetScan software was used to predict the targets of deregulated miRNAs. Western blotting and luciferase assay were performed to verify the targets of these miRNAs.RESULTS： Ten up-regulated miRNAs （miR-217, miR- 518b, miR-517c, miR-520g, miR-519a, miR-522, miR- 518e, miR-525-3p, miR-512-3p, and miR-518a-3p） and 11 down-regulated miRNAs （miR-138, miR-214, miR-214#, miR-199a-5p, miR-433, miR-511, miR-592, miR-483-3p, miR-483-5p, miR-708 and miR-1275） were identified by Taqman miRNAs array and confirmed quantitatively by reverse transcription polymerase chain reaction in HCC and adjacent non-tumor tissues. GO and KEGG pathway analysis revealed that ＂regulation of actin cytoskeleton＂ and ＂pathway in cancer＂ are most likely to play critical roles in HCC tumorigenesis. MiR- 519a and ribosomal protein S6 kinase polypeptide 3 （RPS6KA3） were predicted as the most significant can-didates by miRNA-mRNA network. In addition, cyclin D3 （CCND3） and clathrin heavy chain （CHC）, usually up-regulated in HCC tissues, were validated as the di- rect target of miR-138 and miR-199a-5p, respectively.
基金supported by the International Science and Technology Cooperation Plan of Guizhou Province,China[(2013)7027]the National Natural Science Foundation of China(81471137 and 31730040).
文摘Multiple sclerosis(MS)is a chronic and incurable autoimmune neurodegenerative disease of the central nervous system.Although the symptoms of MS can be managed by vitamin D3 treatment alone,this condition cannot be completely eradicated.Thus,there might be unknown factors capable of regulating the vitamin D receptor(VDR).Genome-wide analysis showed that miRNAs were associated with VDRs.We sought to determine the role and mechanism of action of miRNA-125a-5p and VDRs in a model of MS,mice with experimental autoimmune encephalomyelitis(EAE),which was induced by myelin oligodendrocyte glycoprotein 35–55 peptides.EAE mice showed decreased mean body weight but increased mean clinical scores compared with vehicle or control mice.And inflammatory infiltration was found in the lumbosacral spinal cord of EAE mice.In addition,VDR expression was significantly lower while the expression of miR-125a-5p was markedly higher in the spinal ventral horn of EAE mice than in vehicle or control mice.Importantly,activation of VDRs by paricalcitol or inhibition of miR-125a-5p by its antagomir markedly decreased the mean clinical scores in EAE mice.Interestingly,VDR and miR-125a-5p were co-localized in the same neurons of the ventral horn.More importantly,inhibition of miR-125a-5p remarkably blocked the decrease of VDRs in EAE mice.These results support a critical role for miR-125a-5p in modulating VDR activity in EAE and suggest potential novel therapeutic interventions.
