Long noncoding RNA MIR100HG regulates inflammatory response by interacting with RNA‐binding protein Quaking in periodontitis

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.