LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma.

ABSTRACT: Long non-coding RNAs (lncRNAs) play a crucial role in macrophage development but little is known about their role in asthma. Here, we investigated the role of lncRNA lncTRPM2-AS in asthma and found that lncTRPM2-AS participates in the promotion of macrophage inflammation. Downregulation of lncTRPM2-AS promoted apoptosis and inhibited proliferation and production of cytokines including IL-1β, IL-4, IL-6, IL-10, TNF-α, and TGF-β. RNA-immunoprecipitation and mass spectrometry indicated that the protein TRPM2 interacted with both lncTRPM2-AS and the E3 ubiquitin ligase TRIM21. LncTRPM2-AS silencing enhanced the interaction between TRIM21 and TRPM2, resulting in elevated levels of ubiquitin-related degradation of TRPM2. Mutation analysis indicated that TRPM2 K1218 is a key site for TRIM21-dependent ubiquitination. Downregulation of lncTRPM2-AS significantly decreased intracellular calcium levels by restraining TRPM2 protein expression, which in turn decreased ROS levels and increased autophagy to promote macrophage apoptosis and reduce cytokine production, together inhibiting macrophage inflammation. Taken together, our findings demonstrate that lncTRPM2-AS blocks the ubiquitination of TRPM2 via TRIM21 and inhibits autophagy-induced apoptosis which may contribute to macrophage inflammation in asthma.

SUBMITTER: Li X 

PROVIDER: S-EPMC8668916 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature