lncRNA IGHC<i>γ</i>1 Acts as a ceRNA to Regulate Macrophage Inflammation via the miR-6891-3p/TLR4 Axis in Osteoarthritis

Abstract

Accumulating data have implicated that long noncoding RNA (lncRNA) plays an important role in osteoarthritis (OA), which may function as a competitive endogenous RNA (ceRNA) of microRNAs (miRNAs). lncRNA IGHC<i>γ</i>1 has been demonstrated to regulate inflammation and autoimmunity. Nonetheless, the altering effect of IGHC<i>γ</i>1 in OA remains unclear. This study is aimed at investigating the mechanism and function of lncRNA IGHC<i>γ</i>1 in OA. CCK-8, EdU, and transwell assays were used to estimate macrophage proliferation and migration. Fluorescence in situ hybridization (FISH) was performed to estimate the local expression of lncRNA IGHC<i>γ</i>1 in macrophages. Luciferase reporter assay was adopted to validate the ceRNA role of IGHC<i>γ</i>1 as miRNA sponge. lncRNA IGHC<i>γ</i>1 was primarily localized in macrophage cytoplasm and upregulated in OA. miR-6891-3p inhibited macrophage proliferation, migration, and inflammatory response by targeting TLR4, while lncRNA IGHC<i>γ</i>1 promoted TLR4 expression by functioning as a ceRNA for miR-6891-3p through the NF-<i>κ</i>B signal in macrophages. This study strongly supports that lncRNA IGHC<i>γ</i>1 regulates inflammatory response via regulating the miR-6891-3p/TLR4/NF-<i>κ</i>B axis in macrophages.