title: MicroRNAs and their target genes in gingival tissues.
abstract: To gain insights into the in vivo function of miRNAs in the context of periodontitis, we examined the occurrence of miRNAs in healthy and diseased gingival tissues and validated their in silico-predicted targets through mRNA profiling using whole-genome microarrays in the same specimens. Eighty-six individuals with periodontitis contributed 198 gingival papillae: 158 'diseased' (bleeding-on-probing, PD > 4 mm, and AL ≥ 3 mm) and 40 'healthy' (no bleeding, PD ≤ 4 mm, and AL ≤ 2 mm). Expression of 1,205 miRNAs was assessed by microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted miRNA targets were identified and tested for enrichment by Gene Set Enrichment Analysis (GSEA). Enriched gene sets were grouped in functional categories by DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were significantly differentially expressed between healthy and diseased gingiva. Four miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa-miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2-fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60 enriched miRNA gene sets with target genes involved in immune/inflammatory responses and tissue homeostasis. This is the first study that concurrently examined miRNA and mRNA expression in gingival tissues and will inform mechanistic experimentation to dissect the role of miRNAs in periodontal tissue homeostasis and pathology.
authors.affiliation: Division of Periodontics, Section of Oral and Diagnostic Sciences, Columbia University College of Dental Medicine, 630 West 168 St., PH-7 E 110, New York, NY 10032, USA.
authors.forename: C
authors.initials: C
authors.lastname: Stoecklin-Wasmer
authors.forename: P
authors.initials: P
authors.lastname: Guarnieri
authors.forename: R
authors.initials: R
authors.lastname: Celenti
authors.forename: R T
authors.initials: RT
authors.lastname: Demmer
authors.forename: M
authors.initials: M
authors.lastname: Kebschull
authors.forename: P N
authors.initials: PN
authors.lastname: Papapanou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020869:Gene Expression Profiling; D005881:Gingiva / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D010518:Periodontitis / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D055815:Young Adult
chemical_list: C524942:MIRN155 microRNA, human; C546703:MIRN203 microRNA, human; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger