Downregulation of miRNA‐26 in chronic periodontitis interferes with innate immune responses and cell migration by targeting phospholipase C beta 1

Abstract

Aim: To evaluate the potential role of miR-26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization.Materials and Methods: Expression of miR-26a-5p and miR-26b-5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non-surgical (scaling and root planing) therapy by RT-qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation.Cytokine expression was assessed in miR-26a-5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans or Pg lipopolysaccharide (LPS). Wound closure assays were performed in cells transfected with miR-26a-5p, while the impact on cytoskeletal organization was assessed by F-actin staining.Results: miR-26a-5p and miR-26b-5p were downregulated in diseased gingiva and restored 4-6 weeks post-therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase C beta 1 as a bona fide novel target exhibiting antagonistic expression pattern in disease and post-therapy cohorts. miR-26a-5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement.Conclusions: Downregulated miR-26a-5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defence and wound healing.

Non‐coding RNA LINC01010 regulates macrophage polarization and innate immune functions by modulating NFκB signaling pathway

“…P. gingivalis (Pg) and A. actinomycetemcomitans (Aa) are two key etiological bacteria involved in periodontal pathogenesis (Grenier & Tanabe, 2010; Guentsch et al, 2009; Schröder et al, 2023). Information on lncRNA involvement in PD pathogenesis and the role of periodontal bacteria in lncRNA expressional perturbation remains poorly understudied (Ahmad et al, 2023; Sayad et al, 2020; Uttamani et al, 2023). Therefore, we examined whether the expression of candidate lncRNAs is impaired in PD.…”

“…We next asked whether these lncRNAs are important in innate immune regulation. LncRNA expression was quantified in response to LPS from Pg (a TLR2/4/6 ligand), Aa (a TLR4 ligand), two key etiological bacterial pathogens causing PD, and E. coli (a TLR4 ligand), a non-oral bacterium (Uttamani et al, 2023). M1 and M2 Mφ were challenged with Pg-LPS (1 µg/mL), Aa-LPS (100 ng/mL) and E. coli LPS (100 ng/mL) for 4 and 24 h and the expression of candidate lncRNAs were examined by RT-qPCR.…”

Analyzing Pooled Microarray Gene Expression Data to Uncover Common Pathways in Periodontitis and Oral Squamous Cell Carcinoma from the Gene Expression Omnibus

“…This dysregulation could contribute to the progression and persistence of inflammation in the periodontal microenvironment. [ 26 ] Conversely, in the OSCC scenario, miR-26a-5p exhibits an upregulated expression pattern. [ 27 ] miR-129-2-3p shows versatile effects, from suppressing tumor growth and metastasis to participating in cell differentiation and influencing neurological disorders.…”

The miR‐302/367 cluster: Aging, inflammation, and cancer

“…The modules are available in a variety of formats. A variety of different algorithmic tools are available to identify potential miRNA targets, such as Targetscan, 104 miRWalk, 105 miRBase, 106 DIANAmT, miRanda, miRDB, PICTAR5, PITA, and RNA22. In addition, miRNA high‐throughput microarrays, RNA pull‐down assays, luciferase reporter gene assays, real‐time polymerase chain reaction, and western blot analysis are the methods to study miRNA targets.…”