Long non-coding RNA NEAT1 functions as a competing endogenous RNA to regulate S100A9 expression by sponging miR-196a-5p in rosacea

Abstract

BackgroundRosacea is a complex, chronic, and recurrent dermatologic condition that adversely affects quality of life and self-esteem. However, clinical relevance and molecular mechanisms underlying NEAT1 influence in rosacea remain unclear. ObjectiveThe present study aims to investigate the dynamics and influences of lncRNAs, miRNAs, and mRNAs in rosacea patients, and to explore the impacts of NEAT1 treatments on miR-196a-5p and S100A9 expression in LL37-treated HaCaT cells. MethodsRNA-sequencing of skin tissues from rosacea patients and integrative analyses facilitated comprehensive exploration of lncRNA, mRNA, and miRNA networks. We identified differentially expressed lncRNAs in paired rosacea afflicted and non-lesioned tissues by hub lncRNAs in the ceRNA network. The role of NEAT1 in LL37-treated HaCaT cells was identified by in vitro experiments. ResultsThere were 237 lncRNAs, 38 miRNAs, and 1784 mRNAs in lesioned skin compared to non-lesioned skin in six rosacea patients. NEAT1 was upregulated in rosacea skin and in LL37-treated HaCaT cells. Moreover, inflammatory damage was able to be reduced in vitro after knockdown of NEAT1. Finally, NEAT1 was able to directly interact with miR‐196a-5p, and downregulating miR‐196a-5p was efficient in reversing the influence of NEAT1 siRNA on S100A9. ConclusionWe have completed the first genome-wide lncRNA profiling of paired lesioned and non-lesioned samples from rosacea afflicted patients. The NEAT1/miR-196a-5p/S100A9 axis may have played an important role in the dynamics underlying inflammatory responses of rosacea. NEAT1 may have functioned as a competing endogenous RNA which regulated inflammatory responses in rosacea by sponging miR-196a-5p and upregulating S100A9 expression.