Long noncoding RNA MIR100HG regulates inflammatory response by interacting with RNA-binding protein Quaking in...

Long noncoding RNAs (lncRNAs) are emerging regulators of periodontal inflammation. This study investigates the role of lncRNA MIR100HG in periodontitis and its interaction with the RNA-binding protein Quaking (QKI).

In vitro, human gingival fibroblasts (HGFs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (Pg.LPS, 200 ng/mL, 24 h). In vivo, ligature-induced periodontitis was established in mice. RNA sequencing, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and Western blotting were employed to dissect molecular mechanisms.

MIR100HG was downregulated in inflamed gingival tissues (RNA-seq). FISH and Subcellular RNA fractionation analysis confirmed MIR100HG was primarily localized in the nucleus of HGFs. Knockdown of MIR100HG attenuated Pg.LPS-stimulated inflammation (interleukin [IL]-1β, IL-6 and tumor necrosis factor alpha [TNF-α]) in HGFs, while overexpression exacerbated cytokine release. The interaction between QKI and MIR100HG was identified by RNA immunoprecipitation assays. QKI silencing reversed anti-inflammatory effects of MIR100HG knockdown, linking this axis to nuclear factor kappa B (NF-κB) activation. In mice, knockdown of MIR100HG significantly mitigated alveolar bone loss and the levels of inflammatory markers.

This study identifies MIR100HG as a key lncRNA in periodontitis, showing its downregulation in human and murine models. MIR100HG knockdown alleviates periodontal inflammation via a QKI-mediated feedback loop, underscoring its potential as a therapeutic target for periodontitis management.

Long non-coding RNAs (lncRNAs) are emerging as critical regulators in the pathogenesis of periodontitis, yet the functional roles of most differentially expressed lncRNAs remain poorly understood. In this study, we identified MIR100HG as a significantly downregulated lncRNA in periodontitis-affected gingival tissues through RNA transcriptome sequencing. Functional experiments revealed that MIR100HG knockdown attenuates Porphyromonas gingivalis lipopolysaccharide (Pg.LPS) -induced inflammation in human gingival fibroblasts (HGFs), as evidenced by reduced levels of proinflammatory cytokines (interleukin [IL] -1β, IL-6, and tumor necrosis factor [TNF] -α), whereas MIR100HG overexpression exacerbates inflammatory responses. Mechanistically, MIR100HG activates the nuclear factor kappa B (NF-κB) signaling pathway by interacting with the RNA-binding protein Quaking (QKI), a known suppressor of NF-κB. This interaction forms a negative feedback loop that regulates inflammatory responses. Importantly, MIR100HG knockdown alleviated periodontal inflammation and bone loss in periodontitis mouse model, further supporting its pivotal role in disease progression. Our findings demonstrate that MIR100HG modulates periodontal inflammation through a QKI- mediated mechanism, highlighting its potential as a therapeutic target for periodontitis. This study provides novel insights into lncRNA-mediated immune regulation and highlights its potential as a therapeutic target for managing periodontitis.