Lnc‐CHRM4‐2:1 Inhibits M2 Polarization and Efferocytosis of Macrophages by Downregulating MerTK and SLC2A1 in Rheumatoid Arthritis

Objective Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Long noncoding RNAs (lncRNAs) have been documented to play important roles in the pathogenesis of RA. This study is aimed to investigate the differentially expressed lncRNAs in RA and explore the underlying roles and mechanisms of RA‐specific lncRNAs. Methods Peripheral blood mononuclear cells (PBMCs) from three RA patients and three healthy controls were detected by transcriptome sequencing analysis. Enrichment analysis was performed to identify the potential functional categories and signal pathways. The expressions of the screened dysregulated lncRNAs in RA were further validated using quantitative real‐time polymerase chain reaction (qRT‐PCR). The effects of the candidate lncRNA lnc‐CHRM4‐2:1 on the proliferation and apoptosis of Raw264.7 cells were determined by cell counting kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU) proliferation assays, and Annexin V‐APC/PI staining flow cytometry assay. qRT‐PCR and western blot were performed to detect the expression of functional molecules related to M1/M2 macrophage polarization and efferocytosis. Results The expression of lnc‐CHRM4‐2:1 was significantly higher in PBMCs of RA patients compared to healthy controls. Lnc‐CHRM4‐2:1 was negatively associated with the level of serum CCP of RA patients, suggesting that it was a RA‐specific lncRNA. Overexpression of lnc‐CHRM4‐2:1 could potentially affect cell proliferation and apoptosis, promote M1 polarization, inhibit M2 polarization, and the mRNA and protein expressions of MerTK and SLC2A1 in Raw264.7 cells. Conclusion Lnc‐CHRM4‐2:1 is an RA‐specific lncRNA, which inhibits macrophage M2 polarization and efferocytosis by downregulating MerTK and SLC2A1. Lnc‐CHRM4‐2:1 may be considered a potential diagnostic biomarker and therapeutic target for RA.