LncRNA ROR promotes NLRP3-mediated cardiomyocyte pyroptosis by upregulating FOXP1 via interactions with PTBP1

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• RNA Biology

Background:

• Viral myocarditis (VMC) is a severe cardiac condition often triggered by viral infections like coxsackievirus B3 (CVB3).
• Cellular pyroptosis, a pro-inflammatory form of programmed cell death, plays a critical role in VMC pathogenesis.
• Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes, including inflammation and cell death.

Purpose of the Study:

• To investigate the role and underlying mechanism of the lncRNA regulators of reprogramming (ROR) in the context of viral myocarditis.
• To determine if ROR influences cardiomyocyte pyroptosis and inflammation during CVB3 infection.

Main Methods:

• Established a VMC cell model using AC16 cells infected with CVB3.
• Quantified cytokine release (IL-1β, IL-18) via ELISA.
• Assessed gene expression using qRT-PCR, cell pyroptosis via flow cytometry and Western blot, and cell viability using CCK-8.
• Investigated molecular interactions using RNA immunoprecipitation (RIP), RNA pulldown, and chromatin immunoprecipitation (ChIP) assays.

Main Results:

• lncRNA ROR expression was significantly upregulated in CVB3-infected AC16 cells.
• Knockdown of ROR enhanced cell viability and reduced IL-1β and IL-18 release, indicating reduced inflammation.
• ROR silencing decreased pyroptosis and levels of pyroptosis-related proteins (NLRP3, ASC, cleaved caspase 1).
• Mechanistically, ROR enhanced mRNA stability of FOXP1 by interacting with PTBP1, and FOXP1 repressed NLRP3 transcription.

Conclusions:

• lncRNA ROR knockdown inhibits CVB3-induced cardiomyocyte inflammation and NLRP3-mediated pyroptosis.
• The protective effect is mediated through the PTBP1/FOXP1 axis, highlighting a novel regulatory pathway.
• ROR may represent a potential therapeutic target for treating viral myocarditis.