Conclusion
HOTTIP facilitates the airway inflammatory response by regulating EFNA3 transcription, providing a therapeutic target for asthma.
Methods
Asthma-related data resources from the Gene Expression Omnibus (GEO) database were extracted to explore the relationships between lncRNAs and asthma, and the lncRNA HOTTIP was identified. The probable effect of HOTTIP on airway inflammation was elaborated by ELISA and histopathologic analysis in OVA-sensitized mice. The online database excavation combined with RNA pull-down, RNA immunoprecipitation, luciferase reporter gene assay, and chromatin immunoprecipitation assay were used to analyze the targeted regulation relationship among HOTTIP, CCCTC-binding factor (CTCF), and Ephrin A3 (EFNA3). In addition, in vivo verification of EFNA3's role in inflammation was conducted in OVA-treated mice.
Objective
Long non-coding RNAs (lncRNAs) function as vital regulators in biologic processes and are dysregulated in various tumors; however, little is known about their role in the inflammatory response in asthma. Therefore, this study aimed to investigate the function of antisense HOXA terminal transcriptional RNA (HOTTIP) and its possible mechanism in the ovalbumin (OVA)-induced inflammatory response in asthmatic mice.
Results
HOTTIP was upregulated in asthmatic mice and downregulating HOTTIP in the mice model of asthma markedly reduced inflammation, and caused less infiltration of inflammatory cells, and secretions of IgE, interleukin (IL)-4, IL-5, and IL-13. Mechanistically, the data indicate that HOTTIP promoted EFNA3 transcription by recruiting CTCF to the EFNA3 promoter. Interestingly, the knockdown of EFNA3 alleviated inflammation in the asthma model.