title: Time Series miRNA-mRNA integrated analysis reveals critical miRNAs and targets in macrophage polarization.
abstract: Polarization of macrophages is regulated through complex signaling networks. Correlating miRNA and mRNA expression over time after macrophage polarization has not yet been investigated. We used paired RNA-Seq and miRNA-Seq experiments to measure the mRNA and miRNA expression in bone marrow-derived macrophages over a time-series of 8 hours. Bioinformatics analysis identified 31 differentially expressed miRNAs between M1 and M2 polarized macrophages. The top 4 M1 miRNAs (miR-155-3p, miR-155-5p, miR-147-3p and miR-9-5p) and top 4 M2 miRNAs (miR-27a-5p, let-7c-1-3p, miR-23a-5p and miR-23b-5p) were validated by qPCR. Interestingly, M1 specific miRNAs could be categorized to early- and late-response groups, in which three new miRNAs miR-1931, miR-3473e and miR-5128 were validated as early-response miRNAs. M1 polarization led to the enrichment of genes involved in immune responses and signal transduction, whereas M2 polarization enriched genes involved in cell cycle and metabolic processes. C2H2 zinc-finger family members are key targets of DE miRNAs. The integrative analysis between miRNAs and mRNAs demonstrates the regulations of miRNAs on nearly four thousand differentially expressed genes and most of the biological pathways enriched in macrophage polarization. In summary, this study elucidates the expression profiles of miRNAs and their potential targetomes during macrophage polarization.
authors.affiliation: Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA.|Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Liangqun
authors.initials: L
authors.lastname: Lu
authors.affiliation: Center for Cardiovascular Research John A. Burns School of Medicine, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: McCurdy
authors.affiliation: Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA.|Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Sijia
authors.initials: S
authors.lastname: Huang
authors.affiliation: Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA.|Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Genomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
authors.forename: Karolina
authors.initials: K
authors.lastname: Peplowska
authors.affiliation: Genomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
authors.forename: Maarit
authors.initials: M
authors.lastname: Tiirikainen
authors.affiliation: Center for Cardiovascular Research John A. Burns School of Medicine, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Boisvert
authors.affiliation: Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA.|Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Lana X
authors.initials: LX
authors.lastname: Garmire
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D005269:Femur / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D058977:Molecular Sequence Annotation; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013977:Tibia / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger