hsa-miR-374b-5p regulates expression of the gene U2AF homology motif (UHM) kinase 1

Mueller R., Bajric D., Keceli H. G., Keller A., Dommisch H., El Sharawy A., ...Daha Fazla

JOURNAL OF PERIODONTAL RESEARCH, cilt.56, sa.6, ss.1028-1036, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 56 Sayı: 6
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1111/jre.12913
  • Dergi Adı: JOURNAL OF PERIODONTAL RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1028-1036
  • Anahtar Kelimeler: blood, inflammation, microRNA, periodontitis, tobacco, MICRORNA EXPRESSION, LUNG-CANCER, PERIODONTITIS, PREVALENCE, PROFILES, MEDIATE, MIRNAS, ADULTS, TIME
  • Hacettepe Üniversitesi Adresli: Hayır

Özet

Objective We aimed to identify a microRNA (miRNA) that is significantly upregulated in blood and in cells of the oral mucosa upon exposure to the periodontitis main risk factors oral inflammation and tobacco smoke, to subsequently identify its target gene and to describe the molecular mechanism of gene regulation. Background miRNAs are associated with many disorders. Array-based miRNA expression studies indicated a number of differentially expressed miRNAs in the pathology of oral diseases. However, these miRNAs mostly lacked replication, and their target genes have remained unknown. Methods 863 miRNAs were analyzed in blood from 18 PD cases and 70 controls (Geniom Biochip). Selected miRNAs were analyzed for upregulation in the inflamed oral mucosa of PD patients using published miRNA expression profiling studies from gingival cells. hsa-miR-374b-5p mimic was overexpressed in primary gingival fibroblasts (pGFs) from 3 donors, and genome-wide mRNA expression was quantified (Clarion Array). Gene-specific regulation was validated by qRT-PCR and Luciferase activity in HeLa cells. Results hsa-miR-374b-5p showed >twofold change (FC) in 3 independent studies performed in blood, gingival tissues, and cells. After hsa-miR-374b-5p overexpression, genome-wide expression analysis showed UHMK1 as top 1 downregulated gene in pGFs (p = 2.5 x 10(-04), fold change = -1.8). Reporter genes demonstrated that hsa-miR-374b-5p downregulates mRNA levels (p = .02; FC = -1.5), leading to reduction in protein activity (p = .013, FC = -1.3). Conclusions hsa-miR-374b-5p is upregulated in blood and ginvial cells exposed to oral inflammation and tobacco smoke and regulates UHMK1, which has a role in osteoclast differentiation.