Objective: The purpose of this design was to explore the specific role and related mechanism of long noncoding RNA (lncRNA) regulators of reprogramming (ROR) in viral myocarditis (VMC).
Methods: AC16 cells were infected with coxsackievirus B3 (CVB3) to establish a VMC cell model in vitro. The release of interleukin (IL)-1β and IL-18 was evaluated by enzyme-linked immunosorbent assay (ELISA). Gene expression was calculated using quantitative real-time (qRT)-PCR. Cell pyroptosis was determined by flow cytometry and Western blot assays. Cell counting Kit-8 (CCK-8) detected cell viability. The molecular associations were verified by employing RNA immunoprecipitation (RIP), RNA pulldown and chromatin immunoprecipitation (ChIP) assays.
Results: The lncRNA ROR was more highly expressed in CVB3 virus-infected AC16 cells than in controls. Knockdown of ROR markedly rescued cell viability and reduced the release of IL-1β and IL-18, cell pyroptosis and pyroptotic proteins such as NLRP3, ASC and cleaved caspase 1. Mechanistically, ROR destroyed the mRNA stability of Forkhead Box P Factor 1 (FOXP1) by binding polypyrimidine tract binding protein 1 (PTBP1). FOXP1 repressed the transcription of NLRP3 by directly interacting with its promoter. Importantly, coinhibition of FOXP1 impeded the protective role of ROR silencing in CVB3-infected AC16 cells.
Conclusion: In conclusion, these findings elucidated that ROR knockdown inhibited CVB3-induced cardiomyocyte inflammation and NLRP3-mediated pyroptosis by regulating the PTBP1/FOXP1 axis, implying that ROR might be a new inducer in CVB3-infected VMC.
Keywords: Coxsackievirus B3; FOXP1; Pyroptosis; Viral myocarditis; lncRNA ROR.
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