title: Identification of differentially expressed microRNAs and their PKC-isoform specific gene network prediction during hypoxic pre-conditioning and focal cerebral ischemia of mice.
abstract: We previously reported the involvement of conventional protein kinase C (cPKC) βII, γ, novel PKC (nPKC) ε and their interacting proteins in hypoxic pre-conditioning (HPC)-induced neuroprotection. In this study, the large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs and their PKC-isoform specific gene network in mouse brain after HPC and 6 h middle cerebral artery occlusion (MCAO). We found 4 up-regulated and 13 down-regulated miRNAs in the cortex of HPC mice, 26 increased and 39 decreased gene expressions of miRNAs in the peri-infarct region of 6 h MCAO mice, and 11 up-regulated and 22 down-regulated miRNAs in the peri-infarct region of HPC and 6 h MCAO mice. Based on Diff Score, 19 differentially expressed miRNAs were identified in HPC and 6 h MCAO mouse brain. Then the miRNA-gene-network of 19 specified miRNAs target genes of cPKCβII, γ and nPKCε-interacting protein was predicted by using bioinformatics analysis of genome databases. Furthermore, the down-regulated miR-615-3p during HPC had a detrimental effect on the oxygen-glucose deprivation (OGD)-induced N2A cell injury. These results suggested that the identified 19 miRNAs, notably miR-615-3p, might target these genes of cPKCβII, γ and nPKCε-interacting proteins involved in HPC-induced neuroprotection.
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences and School of Biomedical Engineering, Capital Medical University, Beijing, China.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Liu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Peng
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Dongguo
authors.initials: D
authors.lastname: Li
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000503:physiopathology*; D002461:Cell Line, Transformed; D002470:Cell Survival; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009447:Neuroblastoma; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D035683:MicroRNAs; D020033:Protein Isoforms; D011493:Protein Kinase C