Circ_0075932 in adipocyte-derived exosomes induces inflammation and apoptosis in human dermal keratinocytes by directly binding with PUM2 and promoting PUM2-mediated activation of AuroraA/NF-κB pathway

Abstract

It remains unclear why obese persons displayed a slower wound healing rate than the normal. In this study, we found that has_circ_0075932, a single-exon circular RNA, was outstandingly expressed in human normal adipose tissue and overexpressed in burned skin of obese persons compared with that of non-obese persons. Circ_0075932 overexpression or silencing in dermal keratinocytes had no obvious effect on cell behaviors, unless dozens of times overexpression, since its basal expression level in keratinocytes is too low. However, the exosome released from circ_0075932-overexpressing adipocytes displayed a significantly promoting effect on inflammation and apoptosis in dermal keratinocytes. Then, in our mechanism exploration, we found that circ_0075932 directly bound with the RNA-binding protein PUM2, which was reported to positively regulated AuroraA kinase, thus activating the NF-κB pathway. Moreover, either silencing PUM2, silencing AuroraA, or blockade of NF-κB activation, could abrogate the promoting effect of adipocyte-derived exosomal circ_0075932 on cell inflammation and apoptosis.

Keywords: Adipocyte-derived exosome; AuroraA/NF-κB pathway; Dermal keratinocytes; PUM2; RNA-Protein interaction; circ_0075932.