Preparation of a miR-155-activating Nucleic Acid Nanoflower to Study the Molecular Mechanism of miR-155 in Inflammation

Background: At present, the molecular mechanisms underlying inflammation remain unclear. In recent years, research on inflammation has focused on stimulating cell inflammation by using external pathogens such as LPS or inflammatory factors. To investigate the molecular mechanism of inflammation from a new perspective, we designed a nucleic acid nanoflowers (NFs) complex to directly activate inflammatory genes to study the inflammatory response without the need for external microbial factors to trigger an inflammatory response. ResultsAn RNAa-type target gene-activated NF was designed. Human umbilical vein endothelial cells (HUVECs) were transfected with NFs carrying saRNAs to directly co-activate microRNA (miR)-155 and SHIP1 genes. Inflammatory gene and protein expression in the HUVECs were evaluated to assess whether miR-155 overexpression can trigger inflammation. After RNAa-type NFs were transferred into HUVECs, the expression of miR-155 and pro-inflammatory and cancer-related factors increased, anti-inflammatory factors were reduced, cell proliferation increased, and cell migration was promoted. IL-1β protein levels were decreased and SHIP1 expression was downregulated. When miR-155 and its target SHIP1 were both activated, the expression of both was unaltered, maintaining cell homeostasis. ConclusionMiR-155 and its target genes act as a molecular switch role in the development of inflammation.