MicroRNAs and Their Target Genes in Gingival Tissues

Abstract

A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. AbstrActTo 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, hsamiR-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.

MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients

“…Surprisingly, these three reports yielded completely different results, probably because of differences in ethnicity and experimental conditions. However, hsa-miR-223 was overexpressed in inflamed gingiva in both this study and the American study (12). miR-223 is involved in many types of cancer, inflammatory diseases, autoimmune diseases, and in pathological processes such as leukemia, RA, and cardiovascular disease (19)(20)(21)(22)(23).…”

“…A study of Americans found 25 miRNAs that were upregulated (>2.63-to 1.48-fold) in inflamed gingiva. The three most overexpressed miRNAs were hsa-miR-451, hsa-miR-223, and hsa-miR-486-5p (12). Surprisingly, these three reports yielded completely different results, probably because of differences in ethnicity and experimental conditions.…”

“…Three previous studies compared miRNA expression in periodontitis and healthy gingival tissues (10)(11)(12). A hsa-miR-379 hsa-miR-199a-5p hsa-miR-214 hsa-miR-30a hsa-miR-886-3p hsa-miR-125b-2* hsa-miR-222 hsa-miR-26a hsa-miR-193a-3p hsa-miR-127-3p hsa-miR-381 hsa-miR-154 hsa-miR-30a* hsa-miR-181a hsa-miR-34a hsa-miR-376c hsa-miR-376a hsa-miR-125b hsa-miR-100 hsa-miR-218 hsa-miR-99a hsa- let-7c 37 408 301 536 0 0 210 184 207 13 233 129 536 626 387 254 199 229 28 931 19 12 study of Chinese found that five miRNAs (hsa-miR-126*, hsa-miR-190, hsa-miR-20a, hsa-miR-32, and hsa-miR-362-3p) were greatly upregulated (>5-fold) in inflamed gingival tissues, as compared with healthy gingival tissues; 86 miRNAs were slightly upregulated (2-to 5-fold) (10).…”

“…Several studies indicate that miRNAs are key regulators of cell growth and differentiation, carcinogenesis, rheumatoid arthritis (RA), and inflammation (6)(7)(8)(9). Three recent studies compared miRNA profiles in healthy and periodontitis gingival tissues (10)(11)(12). Other studies found that comorbidity of periodontitis with obesity was associated with locally upregulated expression of Journal of Oral Science, Vol.…”

microRNA Expression in Rat Apical Periodontitis Bone Lesion

“…Other than the global intervention of microRNA machinery, miR-155 (65), miR146a (66), and miR-223 (28,67) were identified to be related with osteoclastogenesis. miRNAs were identified in periodontitis gingiva as well (68). Nevertheless, a lack of systemic analysis of microRNAs involvement in apical periodontitis is obvious.…”