YTHDC1-Modified m6A Methylation of Hsa_circ_0102678 Promotes Keratinocyte Inflammation Induced by Cutibacterium acnes Biofilm through Regulating miR-146a/TRAF6 and IRAK1 Axis

• Published in: Journal of innate immunity 2023-01, Vol.15 (1), p.822-835
• Main Authors: Zhou, Meng, Liu, Yuzhen, Xu, Haoxiang, Chen, Xu, Zheng, Nana, Duan, Zhimin, Ge, Yiping, Li, Dongqing, Lin, Tong, Zeng, Rong, Chen, Qing, Li, Min
• Format: Article
• Language: English
• Subjects: acne; Acne Vulgaris - genetics; Biofilms; Cell Proliferation; circrna; Humans; In Situ Hybridization, Fluorescence; inflammation; Inflammation - genetics; Interleukin-1 Receptor-Associated Kinases - genetics; m6a; Methylation; MicroRNAs - genetics; mir-146a; Nerve Tissue Proteins; Research Article; RNA Splicing Factors; RNA, Circular - genetics; TNF Receptor-Associated Factor 6 - genetics; ythdc1
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000534704

Abstract Introduction: CircRNAs are closely related to many human diseases; however, their role in acne remains unclear. This study aimed to determine the role of hsa_circ_0102678 in regulating inflammation of acne. Methods: First, microarray analysis was performed to study the expression of circRNAs in acne. Subsequently, RNase R digestion assay and fluorescence in situ hybridization assay were utilized to confirm the characteristics of hsa_circ_0102678. Finally, qRT-PCR, Western blotting analysis, immunoprecipitation, luciferase reporter assay, circRNA probe pull-down assay, biotin-labeled miRNA pull-down assay, RNA immunoprecipitation assay, and m6A dot blot assay were utilized to reveal the functional roles of hsa_circ_0102678 on inflammation induced by C. acnes biofilm in human primary keratinocytes. Results: Our investigations showed that the expression of hsa_circ_0102678 was significantly decreased in acne tissues, and hsa_circ_0102678 was a type of circRNAs, which was mainly localized in the cytoplasm of primary human keratinocytes. Moreover, hsa_circ_0102678 remarkably affected the expression of IL-8, IL-6, and TNF-α, which induced by C. acnes biofilm. Importantly, mechanistic studies indicated that the YTHDC1 could bind directly to hsa_circ_0102678 and promote the export of N6-methyladenosine-modified hsa_circ_0102678 to the cytoplasm. Besides, hsa_circ_0102678 could bind to miR-146a and sponge miR-146a to promote the expression of IRAK1 and TRAF6. Conclusion: Our findings revealed a previously unknown process by which hsa_circ_0102678 promoted keratinocyte inflammation induced by C. acnes biofilm via regulating miR-146a/TRAF6 and IRAK1 axis.