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Role of LINC00240 on T-helper 9 differentiation in Allergic Rhinitis through influencing DNMT1-dependent methylation of PU.1
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  • Jianguo Liu,
  • Xunshuo Jiang,
  • Ke Liu,
  • Jianjian Deng,
  • Yi Qiu,
  • Wan Wei,
  • Chunping Yang
Jianguo Liu
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Xunshuo Jiang
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Jianjian Deng
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Chunping Yang
Nanchang University Second Affiliated Hospital

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Background Allergic rhinitis (AR) is a common allergic disease with increasing prevalence globally. However, the molecular mechanism underlying AR pathogenesis remains largely undefined. Methods Samples of peripheral blood and nasal mucosa from patients with AR, as well as the ovalbumin-induced AR mice model was obtained. qRT-PCR and western blot were used to detect the expression of LINC00240, miR-155-5p, PU.1 and other key molecules. ELISA assay and flow cytometry were employed to evaluate the secretion of IL-9 and T-helper 9 (Th9) cell ratio, respectively. Bioinformatics analysis, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and luciferase reporter assays were employed to further elucidate the regulatory network of LINC00240/miR-155-5p/DNMT1. The methylation of PU.1 promoter was assessed by methylation-specific PCR (MSP). This signaling axis was finally confirmed in the AR mice model. Results LINC00240 was downregulated, while miR-155-5p and PU.1 were upregulated in the peripheral blood and nasal mucosa of AR patients, as well as in the AR mice. This was accompanied with the increased ratio of Th9 cells and elevated IL-9 secretion. Mechanistically, LINC00240 served as a miR-155-5p sponge, and DNMT1 was a target of miR-155-5p. In addition, DNMT1 mediated the methylation of PU.1 promoter. In vivo studies verified that LINC00240 mitigated AR progression, possibly via miR-155-5p/DNMT1/PU.1-dependent Th9 differentiation. Conclusion In summary, the involvement of LINC00240 in AR pathogenesis is closely associated with Th9 differentiation through modulating DNMT1-dependent methylation of PU.1 by sponging miR-155-5p.