LncRNA LOXL1-AS1 is transcriptionally activated by JUND and contributes to osteoarthritis progression via targeting the miR-423-5p/KDM5C axis.

Abstract Aims This study focused on investigating the potential role of long non-coding RNA (lncRNA) lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in the progression of osteoarthritis (OA). Materials and methods qRT-PCR assay was applied to detect gene expression, while western blot was performed to measure levels of apoptosis-related proteins. CCK-8, colony formation and TUNEL assays were conducted to explore the functional role of LOXL1-AS1 in OA. ChIP assay was utilized to assess the affinity between JunD proto-oncogene, AP-1 transcription factor subunit (JUND) and LOXL1-AS1 promoter. Mechanism experiments were implemented to investigate the underlying molecular mechanism of LOXL1-AS1. Key findings LOXL1-AS1 was up-regulated in OA cartilage tissues. Silencing LOXL1-AS1 hampered proliferation and inflammation, yet promoting apoptosis in chondrocytes. LOXL1-AS1 was transcriptionally activated by JUND1. LOXL1-AS1 sequestered miR-423-5p and abolished miR-423-5p-mediated repression on lysine demethylase 5C (KDM5C), thus promoted the development of OA. Significance LncRNA LOXL1-AS1 is transcriptionally activated by JUND and facilitates the proliferation and inflammation of chondrocytes via elevating miR-423-5p-mediated KDM5C in OA, which may provide potential therapeutic target for OA.