LINC01410 is an IFN-I-inducible lncRNA that contributes to SLE pathogenesis by enhancing Monocyte-Macrophage...

BackgroundOver-activated Type I interferon (IFN-I) signaling has been widely documented in systemic lupus erythematosus (SLE), but the underlying mechanisms and role of IFN-inducible long noncoding RNAs (lncRNAs) are still being explored. Our study highlights LINC01410 as a novel IFN-α-inducible lncRNA with potential contributions to SLE and LN.Materials and methodsHuman peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors. THP-1, HEK293 T, Jurkat T, and Raji B cell lines were treated with 1000 U/mL IFN-α to evaluate changes in LINC01410 expression. LINC01410 was further overexpressed in THP-1 cells to assess effects on cell proliferation, apoptosis, and macrophage polarization, coupled with measurements of cytokines IL-6 and TNF-α. Additionally, Western blot assays were performed to elucidate LINC01410-associated pathways and protein changes.ResultsLINC01410 was found to be significantly upregulated in SLE PBMCs compared to healthy controls, and its expression was further elevated by IFN-α stimulation in multiple immune cell lines and primary immune cells. Overexpression of LINC01410 in THP-1 cells promoted proliferation, inhibited apoptosis, and drove macrophage differentiation toward an M1 phenotype, with an increase in proinflammatory cytokines such as IL-6 and TNF-α. Enrichment analyses linked LINC01410 to several dysregulated immune processes, consistent with SLE's immunopathology. Cross-dataset validation revealed that LINC01410 modulates key miRNAs, including miR-34a-5p, miR-125a-3p, and miR-185-5p, via the competing endogenous RNA (ceRNA) mechanism, thereby exerting pivotal regulatory effects on critical pathways such as cell cycle regulation, adherens junction, and the PI3K-Akt signaling pathway.ConclusionsOur findings reveal that LINC01410 is an IFN-I-responsive lncRNA that contributes to hyperactive immunity in SLE by modulating monocyte-macrophage function. LINC01410 may represent a novel biomarker and therapeutic target for overcoming disease flares and tissue damage associated with SLE.