Hsa_circ_0105040 promotes Cutbacterium acnes biofilm induced inflammatory via sponge miR-146a in human keratinocyte

Abstract

Abstract Background Circular RNAs (circRNAs) are thought to play a crucial function in controlling gene expression, according to expanding findings. However, the importance of circRNAs in the regulation of acne inflammation is unclear.Methods Microarray analysis has been carried out to investigate circRNAs/miRNAs/mRNAs that express abnormally in acne. RNase R digestion assay is used for confirmation of the hsa_circ_0105040 characteristic. The functional roles of hsa_circ_0105040 on inflammatory response induced by Cutibacterium acnes (C. acnes) biofilm in human primary keratinocytes were revealed by Fluorescence in situ hybridization (FISH), Reverse transcription quantitative (PCR), Western blotting analysis, Immunoprecipitation, Luciferase reporter assay, Biotin-labeled miRNA pull-down assay, RNA immunoprecipitation (RIP).Results We first evaluate the human circRNA expression patterns in acne tissues and find that hsa_circ_0105040 expression is considerably reduced in acne tissues. Moreover, we discover that the majority of hsa_circ_0105040 is found to be localized in the cytoplasm of primary human keratinocytes. Hsa_circ_0105040 overexpression significantly enhances the production of proinflammatory factors (interleukin-8, interleukin-6, and tumor necrosis factor-α). Mechanistic research reveals that the microRNA miR-146a binds to hsa_circ_0105040, which then actively sponges miR-146a to prevent the level of IRAK1 and TRAF6.Conclusions These findings point to hsa_circ_0105040 as a critical circRNA that function as "microRNA sponges" for the controlled inflammatory response in the development of acne. Our findings may provide valuable insights into the progression of acne.