lncRNA AK141955 Acts as a ceRNA to Regulate Macrophage Polarization via the miR-124-3p/Sema6d Axis in Viral Myocarditis

Abstract BackgroundMacrophage polarization is vital for coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). However, only a few empirical studies have focused on exploring the relationship between macrophage polarization and VM. MethodsQuantitative real-time PCR was used to determine the ex-pression levels of AK141955 and miR-124-3p in M1/M2 cells. The functional role of macrophage polarization was investigated by in vitro gene silencing assays. Mechanistically, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to confirm that AK141955 sponged miR-124-3p and alleviated the suppression of target Sema6d expression. ResultsFunctionally, AK141955 knockdown significantly reduced inflammation, inhibited the M1 phenotype, and promoted the M2 phenotype in vitro and in vivo, whereas miR-124-3p inhibitors counteracted these effects. Evidence is presented, showing that AK141955 acted as a “ceRNA” of miR-124-3p to relieve the repressive effect of miR-124-3p on its target Sema6d, then promoted VM development.ConclusionCollectively, our findings reveal that AK141955 functions as a pro-inflammatory factor in pro-moting VM progression through the miR-124-3p/Sema6d axis, providing a solid evidence base for treating VM patients.